Comparison of coronary angioscopic findings 8 months after stent implantation between two kinds of biodegradable polymer-coated and one durable polymer-coated drug-eluting stent.

BACKGROUND: The difference of chronic neointimal conditions of biodegradable polymer-coated and durable polymer-coated drug-eluting stent have not been well investigated. OBJECTIVE: We aimed to compare the angioscopic findings among SYNERGY biodegradable polymer-coated everolimus-eluting stent (BP-EES), ULTIMASTER biodegradable polymer-coated sirolimus-eluting stent (BP-SES), and XIENCE Alpine durable polymer-coated everolimus-eluting stent (DP-EES) 8 months after stent implantation. METHODS: Patients who underwent implantation of BP-EES (n = 30), BP-SES (n = 26), or DP-EES (n = 21) in Osaka Rosai Hospital from December 2015 to April 2017 were retrospectively enrolled. Coronary angioscopic evaluation including dominant grade of neointimal coverage (NIC) over the stent, maximum yellow plaque grade, and existence of red thrombi were performed 8 months after stent implantation. The incidence of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, and target vessel revascularization were assessed 1 year after coronary angioscopic evaluation among the three groups. RESULTS: The patient and lesion characteristics were similar among the three groups. Dominant grade of NIC and maximum yellow plaque grade were not significantly different among BP-EES, BP-SES, and DP-EES groups [mean ± SD, 1.50 ± 0.73, 1.58 ± 0.64, and 1.33 ± 0.48 (P = 0.38) and 0.83 ± 0.59, 0.81 ± 0.75, and 0.95 ± 0.38 (P = 0.68), respectively]. The existence of red thrombi was similar among the three groups [20, 12, and 19% (P = 0.67)]. There was no significant difference in the MACE 1 year after coronary angioscopic evaluation among the three groups [0, 8, and 0% (P = 0.13)]. CONCLUSIONS: Coronary angioscopic findings revealed that BP-EES, BP-SES, and DP-EES produced similar favorable NIC 8 months after stent implantation.

Serial angioscopic evaluation of self-expanding stent graft implantation in superficial femoral artery.

We evaluated Viabahn stent-graft (W.L. Gore & Associates, Flagstaff, AZ, USA) implanted in the superficial femoral artery at 6 months and one year after implantation because the patient felt claudication due to repeated restenosis of bare nitinol stent which was implanted just proximal to the site of Viabahn stent-graft. At 6 months, angioscopy showed severe thrombosis in the stent-graft while the stent-graft was entirely patent. However, at one year, angioscopic evaluation revealed no thrombosis in the stent-graft. She received the same dual antiplatelet therapy. .

A case of a late fatal complication after atrial fibrillation ablation related to a prolonged QT interval unmasked by atrial fibrillation ablation.

A 79-year-old woman with a history of atrial fibrillation (AF) ablation was referred to our hospital for ventricular fibrillation, which was terminated by an automated external defibrillator. The heart rate corrected QT interval was 489 ms. The electrocardiogram monitoring recorded a polymorphic ventricular tachycardia (VT) reproducibly induced by a single morphology premature ventricular contraction (PVC). Therefore, we performed a trigger PVC ablation and implanted an implantable cardioverter defibrillator. No VT events were observed for at least one year after the ablation. A prolonged QT interval after the AF ablation should be carefully noted because it could introduce fatal complications. .

Clinical experience of uninterrupted oral anticoagulants during atrial fibrillation ablation in elderly patients: a comparison with non-elderly patients.

It is unclear whether uninterrupted oral anticoagulants (OACs) are acceptable in elderly patients as compared to non-elderly patients. This study aimed to assess the clinical impact of an uninterrupted OAC strategy during atrial fibrillation (AF) ablation in elderly patients. We enrolled 439 consecutive patients who underwent AF ablation with an uninterrupted OAC strategy at our institute. The incidence of bleeding and thromboembolic complications during the AF ablation or within 4 weeks after and the anticoagulation status during the AF ablation were compared between the elderly (age ≧ 75, n = 144) and non-elderly groups (n = 295). There were 22 bleeding complications in the elderly group and 31 in the non-elderly group (15% vs. 11%, p = 0.162) and 3 major bleeding complications in the elderly group and 2 in the non-elderly group (2% vs. 0.7%, p = 0.336). Thromboembolic events were observed in 1 patient in the elderly group and 2 in the non-elderly group (0.7% vs. 0.7%, p = 1.000). The ACT at the end of the procedure was longer in the elderly group than in the non-elderly group (350 s vs. 341 s, p = 0.007) and the proportion of a prolonged ACT of > 400 s (27% vs. 18%, p = 0.046) was more frequent in the elderly group than non-elderly group. A propensity score matched population excluding the age and body weight, revealed that the anticoagulation status during AF ablation was comparable between the two groups. Thus, in the patients undergoing AF ablation with uninterrupted OAC strategy, bleeding complications in elderly patients were similar to those in non-elderly patients. The anticoagulation status during the procedure in elderly patients was more prolonged than that in non-elderly patients.

Comparison of myocardial injury and inflammation after pulmonary vein isolation for paroxysmal atrial fibrillation between radiofrequency catheter ablation and cryoballoon ablation.

BACKGROUNDS: Several studies have shown the serum high sensitive cardiac troponin I (hs-TnI) a biomarker of myocardium injury, and C-reactive protein (CRP), a biomarker of inflammation, are associated with worse cardiovascular outcomes. We evaluated the relationship between the hs-TnI level in patients with paroxysmal atrial fibrillation (PAF) after pulmonary vein isolation (PVI) and atrial fibrillation (AF) recurrence. METHODS AND RESULTS: We enrolled 263 consecutive PAF patients who underwent PVI from May 2017 to April 2018. We investigated the difference in the relationship between the myocardial injury marker (serum hs-TnI), inflammatory marker (CRP, white blood cell) at 36 to 48 hours after the PVI, and early or late recurrence of AF (ERAF; <3 months and LRAF; from 3 months to 1 year) between the radiofrequency ablation group (R group) and cryoballoon ablation group (C group). The R group consisted of 147 patients and the C groups consisted of 116 patients. The serum hs-TnI level in R group was significantly lower than in the C group (2.33 vs 5.08 ng/mL; P < .001), while the CRP was significantly higher in the R group than C group (2.02 vs 1.10 mg/dL; P < .001). The incidences of an ERAF/LRAF were similar between the two groups. CONCLUSION: Cryoballoon ablation may cause more myocardial injury than radiofrequency catheter ablation, on the contrary, radiofrequency catheter ablation, may cause more inflammation than cryoballoon ablation. However, these phenomena may not affect the recurrence of AF after the PVI in patient with PAF.

Predictors of recurrence after pulmonary vein isolation in patients with normal left atrial diameter.

BACKGROUND: Enlarged left atrium (LA) is an established predictor of recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI), but occasionally recurrences of AF/atrial tachycardia (AT) are experienced in patients with normal left atrial diameter. Therefore, the predictors of AF recurrence and AF triggers were evaluated in patients with normal LA. METHODS: We enrolled 168 patients with normal LA (<40 mm) who underwent PVI. Various predictors were compared, including age, gender, coronary risk factors, brain natriuretic peptide (BNP), medications, echocardiographic parameters, and procedure parameters, between recurrence and nonrecurrence groups. RESULTS: The recurrence group consisted of 50 patients (29.8%). A univariate analysis demonstrated that the ratio of females, high BNP levels, severe tricuspid valve regurgitation (TR), and relapses of AF/AT during catheter ablation (CA) were significantly higher in the recurrence group. Multivariate analyses showed that a high BNP, severe TR, and AF/AT relapses during CA were independent factors associated with AF recurrence. During the second CA sessions, nonpulmonary vein (PV) triggers were therapeutic targets in 18 patients (46.2%), which was higher than that previously reported. CONCLUSION: A high BNP, severe TR and AF/AT relapses during CA may be correlated with AF recurrence after PVI in the patients with normal LA.

Limited efficacy of a figure-of-eight suture for hemostasis after cryoballoon atrial fibrillation ablation with uninterrupted oral anticoagulants.

INTRODUCTION: There are limited data on the efficacy and safety of a figure-of-eight (FoE) suture technique after atrial fibrillation (AF) ablation with uninterrupted oral anticoagulants (OACs). This study evaluated the predictors of bleeding complications at the femoral puncture site after placing a FoE suture to achieve hemostasis after AF ablation with OACs. METHODS: We enrolled 287 consecutive patients who underwent a 1st session of AF ablation using radiofrequency or cryoballoon ablation. Hemostasis of the femoral puncture site was achieved using the FoE suture technique followed by a 4-h bed rest. We compared the various factors that might be correlated with bleeding complications between the patients with bleeding and those with non-bleeding complications. RESULTS: The bleeding complications were observed in 31 patients (11%). In the univariate analysis, cryoballoon ablation (52% vs. 29%, p = 0.009), HAS-BLED score (2.1 ± 1.0 vs. 1.7 ± 1.1, p = 0.030), and the CHA2DS2-VASc score (3.2 ± 1.5 vs. 2.6 ± 1.6, p = 0.049) were significantly associated with bleeding complications at the femoral puncture site. In the multivariate logistic regression analysis after an adjustment for antiplatelet therapy, cryoballoon ablation was an independent predictor of an increased incidence of the bleeding complications at the femoral puncture site (odds ratio 2.77, 95% CI 1.29-6.02, p = 0.009). CONCLUSION: Cryoballoon AF ablation was correlated with bleeding complications after a FoE suture technique with uninterrupted OACs.

A case of a "pseudo jump-up phenomenon" caused by retrograde ventricular-His prolongation.

A 35-year-old woman was referred for treatment of a supraventricular tachycardia. The tachycardia was diagnosed as a slow-fast form of atrioventricular nodal reentrant tachycardia. Radiofrequency ablation targeting the antegrade slow pathway was performed at the posterior septum of the right atrium. After the radiofrequency ablation, ventricular extrastimulus pacing was performed to assess the retrograde slow pathway, which was suggested before the ablation. The prolongation of the VA interval with a 10 ms decrease in the S2 pacing interval was 60 ms and retrograde dual pathways were suspected. However, the HA interval did not change and a prolongation of the VA interval was caused by the prolongation of the VH interval and no additional ablation was required.

Which factors are associated with length of stay in older patients with acute decompensated heart failure with preserved ejection fraction?: AURORA study.

AIM: In heart failure with preserved ejection fraction (HFpEF), it is unclear which factors on admission are correlated with long stays. In contrast, acute decompensated heart failure (ADHF) in older patients is associated with a high risk of a long stay. To manage older ADHF patients with HFpEF, it is important to reveal the risk factors for a long stay on admission. METHODS: We enrolled consecutive older patients (aged >75 years) with HFpEF (ejection fraction ≥50%) who were admitted to control ADHF from May 2014 to April 2016 using the acute heart failure registry in Osaka Rosai Hospital. We compared various factors, including age; sex; body mass index; heart rate; systolic blood pressure (SBP); atrial fibrillation; atherosclerotic risk factors, including dyslipidemia, diabetes mellitus, hypertension, smoking and chronic kidney disease; laboratory data, including brain natriuretic peptide and albumin; and medications, including loop diuretics, on pre-admission between short-stay (<14 days) and long-stay groups. RESULTS: The long-stay group consisted of 122 patients (59.5%). Multivariate analysis showed that male sex, SBP and albumin were independent predictors for long stays. According to the classification and regression tree and receiving operating characteristic curve analysis, all three factors on admission, including male sex, relatively low SBP (<155 mmHg) and hypoalbuminemia (<3.4 g/dL) could well predict the patients that would require long stays (area under curve 0.738). CONCLUSIONS: Among older ADHF patients with HFpEF, male patients with relatively low SBP and hypoalbuminemia on admission should initially undergo more intensive management to reduce the length of stay. Geriatr Gerontol Int 2019; 19: 1084-1087.

Successful ablation for premature ventricular contraction originating from moderator band of morphologic right ventricle in congenitally corrected transposition of great arteries.

A 54-year-old man with congenitally corrected transposition of great arteries (CCTGA) was referred to our hospital for palpitation. 24-hour Holter ECG showed frequent premature ventricular contraction (PVC) and we performed catheter ablation for this PVC. Pace-mapping was performed in morphologic right ventricle (RV) by transaortic approach. Perfect pace-map was achieved in morphologic RV midpart lateral and ablation at this site could eliminate the clinical PVC. After the ablation, by integrating ablation site and 3D mapping, we diagnosed that the clinical PVC was originated from the moderator band (MB) of morphologic RV.

Predictors of cardiac function in acute heart failure patients with mid-range ejection fraction: AURORA study.

AIM: The factors correlated with prognosis in heart failure with mid-range ejection fraction (HFmrEF) is unclear, especially for acute heart failure (AHF) with HFmrEF. Thus, we investigated the factors correlated with the improvement in the ejection fraction (EF) over 1 year in AHF patients with HFmrEF. METHODS AND RESULTS: In Acute Heart Failure Registry in the Osaka Rosai Hospital, we examined 159 consecutive HFmrEF patients out of 1051 HF patients who were admitted to our hospital for AHF from January 2015 to December 2017. We divided them into improved EF (IM) group whose EF improved (≧10%) and non-IM group who had no improvement. We compared the baseline characteristics, echocardiographic data, medications, examinations for ischaemia, invasive treatments, and clinical outcomes between IM group and non-IM group. IM group consisted of 21 patients (20%). IM group had a significantly more de novo heart failure, higher serum albumin (Alb), lower EF, smaller left ventricular dimension during diastole, more frequent coronary angiogram during hospitalization, and coronary intervention. Multivariate analysis revealed that Alb, left ventricular dimension during diastole, and coronary angiogram performed during hospitalization were independently associated with the improvement in the EF. In addition, IM group had less rehospitalizations over 1 year and a greater reduction in the B-type natriuretic peptide level during the follow-up than non-IM group. CONCLUSIONS: In AHF patients with HFmrEF, we should evaluate for any ischaemic heart disease during hospitalization, especially in patients with non-enlarged left ventricular and non-reduced serum Alb. AHF patients with HFmrEF who showed improvement in the EF tended to have better prognosis than those without improvement.

Postmortem late phase histopathology after pulmonary vein isolation using a cryoballoon: A case report.

We report the autopsy case of 68-year-old woman who received cryoballoon (CB) ablation for paroxysmal atrial fibrillation 7 months before death. Both macroscopic and microscopic findings revealed no thrombus formation around pulmonary veins. Previous experimental studies have shown the lower risk of thrombus formation in CB ablation as compared to radiofrequency ablation. Our findings in the human autopsy case may support this merit of CB ablation. To confirm this benefit of CB ablation, further studies regarding histopathology of CB ablation should be performed.

Characteristics of abnormal post-stent optical coherence tomography findings in hemodialysis patients.

AIM: Clinical outcomes after percutaneous coronary intervention (PCI) in hemodialysis (HD) patients are significantly worse than those in non-HD patients. Optical coherence tomography (OCT) is a high resolution imaging modality and provides a detailed assessment of post-interventional abnormal findings that influence worse clinical outcomes. However, little is known about the abnormal post-stent OCT findings in HD patients. Therefore, in this study, we compared the abnormal post-stent OCT findings between HD and non-HD patients. METHODS: One hundred thirty-nine consecutive OCT guided PCI (21 lesions in HD patients and 118 lesions in non-HD patients) were enrolled. We compared the post-stent OCT findings, including the edge dissections, under expansion index (minimum stent area/mean reference area), and stent eccentricity index (minimum stent diameter/maximum stent diameter) between HD and non-HD patients. We also compared the device-oriented clinical events (DoCEs) at 8 months of follow up. RESULTS: There was a significantly higher prevalence of distal edge dissections (16.7% vs. 2.8%, P = 0.011) in HD patients. HD patients had a significantly lower under expansion index (0.76 ± 0.21 vs. 0.85 ± 0.14, P = 0.029) and stent eccentricity index (0.82 ± 0.09 vs. 0.88 ± 0.18, P = 0.018). The cumulative rate of DoCEs was significantly higher in the HD patients (23.8% vs. 5.2%, P = 0.013). CONCLUSIONS: A higher prevalence of distal edge dissections, under expansion and stent eccentricity were detected by the detailed OCT findings in HD patients.

Different Neoatherosclerosis Patterns in Drug-Eluting- and Bare-Metal Stent Restenosis　- Optical Coherence Tomography Study.

BACKGROUND: There are few reports about the differences between drug-eluting stents (DES) and bare metal stents (BMS) in neoatherosclerosis associated with in-stent restenosis (ISR), so we compared the frequency and characteristics of neoatherosclerosis with ISR evaluated by optical coherence tomography (OCT) in the present study. Methods and Results: Between March 2009 and November 2016, 98 consecutive patients with ISR who underwent diagnostic OCT were enrolled: 34 patients had a BMS, 34 had a 1st-generation DES, and 30 had a 2nd-generation DES. Neoatherosclerosis was defined as a lipid neointima (including a thin-cap fibroatheroma [TCFA] neointima, defined as a fibroatheroma with a fibrous cap <65 µm) or calcified neointima. As a result, lipid neointima, TCFA neointima and calcified neointima were detected in 39.8%, 14.3%, and 5.1%, respectively, of all patients. The frequency of neoatherosclerosis was significantly greater with DES than BMS (48.4% vs. 23.5%, P=0.018). The minimum fibrous cap thickness was significantly thicker with DES than BMS (110.3±41.1 µm vs. 62.5±17.1 µm, P<0.001). In addition, longitudinal extension of neoatherosclerosis in the stented segment was less with DES than BMS (20.2±15.1% vs. 71.8±27.1%, respectively, P=0.001). CONCLUSIONS: OCT imaging demonstrated that neoatherosclerosis with ISR was more frequent with DES than BMS and its pattern exhibited a more focal and thick fibrous cap as compared with BMS.

Anti-HB-EGF Antibody-Mediated Delivery of siRNA to Atherosclerotic Lesions in Mice.

For atherosclerotic cardiovascular diseases (ACD), gene therapy may be a potential therapeutic strategy; however, lack of effective and safe methods for gene delivery to atherosclerotic plaques have limited its potential therapeutic applications. To overcome this limitation, we developed a novel antibody-based gene delivery system (anti-HB-EGF/NA vector) by chemically crosslinking antibodies against human heparin-binding epidermal growth factor-like growth factor (HB-EGF). It has been shown to be excessively expressed in human atherosclerotic plaques and NeutrAvidin (NA) for conjugating biotinylated siRNA. Immunofluorescence staining and quantitative flow cytometry analysis using human HB-EGF-expressing cells showed both antibody-mediated selective cellular targeting and efficient intracellular delivery of conjugated biotin-fluorescence. Moreover, we demonstrated antibody-mediated significant and selective gene knockdown via conjugation with anti-HB-EGF/NA vector and biotinylated siRNA (anti-HB-EGF/NA/b-siRNA) in vitro. Furthermore, using high fat-fed human HB-EGF knock-in and apolipoprotein E-knockout (Hbegf hz/hz; Apoe-/-) mice, we demonstrated that the anti-HB-EGF/NA vector, conjugating biotin-fluorescence, increasingly accumulated within the atherosclerotic plaques of the ascending aorta in which human HB-EGF expression levels were highly elevated. Moreover, in response to a single intravenous injection of anti-HB-EGF/NA/b-siRNA in a dose-dependent manner, qPCR analysis of laser-dissected atherosclerotic plaques of the ascending aorta showed significant knockdown of the reporter gene expression. These results suggest that the anti-HB-EGF antibody-mediated siRNA delivery could be a promising delivery system for gene therapy of ACD.

Impact of helical organization on the photovoltaic properties of oligothiophene supramolecular polymers.

Helical self-assembly of functional π-conjugated molecules offers unique photochemical and electronic properties in the spectroscopic level, but there are only a few examples that demonstrate their positive impact on the optoelectronic device level. Here, we demonstrate that hydrogen-bonded tapelike supramolecular polymers of a barbiturated oligo(alkylthiophene) show notable improvement in their photovoltaic properties upon organizing into helical nanofibers. A tapelike hydrogen-bonded supramolecular array of barbiturated oligo(butylthiophene) molecules was directly visualized by STM at a liquid-solid interface. TEM, AFM and XRD revealed that the tapelike supramolecular polymers further organize into helical nanofibers in solution and bulk states. Bulk heterojunction solar cells of the helical nanofibers and soluble fullerene showed a power conversion efficiency of 4.5%, which is markedly high compared to that of the regioisomer of butyl chains organizing into 3D lamellar agglomerates.

Development of a novel one-step production system for injectable liposomes under GMP.

There are few methods available for injectable liposome production under good manufacturing practices (GMP). Injectable liposome production processes under GMP generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. To overcome these limitations, we developed a novel one-step in-line closed liposome production system that integrated all production processes by combining the in-line thermal mixing device with modified counterflow dialysis. To validate the system, we produced liposomal cyclosporine A (Lipo-CsA) and lyophilized the liposomes. The three independent pilot batches were highly reproducible and passed the quality specifications for injectable drugs, demonstrating that this system could be used under GMP. The accelerated stability test suggested that the liposomes would be stable in long-term storage. This one-step system facilitates a fully automated and unattended production of injectable liposomes under GMP.

Ablation of IL-33 gene exacerbate myocardial remodeling in mice with heart failure induced by mechanical stress.

BACKGROUND AND PURPOSE: ST2 is one of the interleukin (IL)-1 receptor family members comprising of membrane-bound (ST2L) and soluble (sST2) isoforms. Clinical trials have revealed that serum sST2 levels predict outcome in patient with myocardial infarction or chronic heart failure (HF). Meanwhile, we and others have reported that ablation of ST2 caused exaggerated cardiac remodeling in both ischemic and non-ischemic HF. Here, we tested whether IL-33, the ligand for ST2, protects myocardium against HF induced by mechanical overload using ligand specific knockout (IL-33-/-) mice. METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33-/- mice than in WT mice. After 8-weeks, IL-33-/- mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33-/- mice than those in WT mice. CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.