Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.

AIM: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. METHODS: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. RESULTS: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. CONCLUSION: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

Impact of Transradial Catheterization on Vascular Function of the Brachial Artery Assessed by Flow-Mediated Dilatation.

BACKGROUND: Few studies have evaluated long-term vascular function after radial access catheterization. Furthermore, the impact of repeated catheterization remains unknown. We investigated flow-mediated dilatation (FMD) of the brachial artery after transradial catheterization. METHODS: We prospectively enrolled 50 patients with suspected coronary artery disease referred for diagnostic coronary angiography. No ad-hoc percutaneous coronary interventions (PCI) had been performed at the time of the index procedure. In 30 patients (63.8%), PCI and/or repeated follow-up diagnostic catheterization were subsequently performed via the radial artery used at the index catheterization. FMD was successfully measured before catheterization, at 24 h after catheterization, and after long-term follow-up (mean, 32 months; range, 24-43) in 47 patients. FMD at follow-up was compared between patients receiving only one procedure and those receiving multiple procedures via the same arteries. RESULTS: FMD was significantly decreased after catheterization and recovered well in long-term follow-up (3.7 ± 1.6%, 3.0 ± 1.7%, and 3.9 ± 1.6%). There was no significant difference in follow-up FMD between the patients undergoing single catheterization and those with multiple procedures (3.4 ± 1.3 vs. 4.3 ± 1.7, p = 0.06). When the patients were divided into two groups according to the median follow-up FMD value, no significant predictive factor was identified for worse FMD. CONCLUSIONS: After transradial catheterization, FMD of the brachial artery temporarily decreased but recovered in long-term follow-up. Recovery of FMD was not jeopardized by repeated catheterization, which suggests the potential of the brachial artery to recover endothelial function after repeated transradial procedures.

Additional cryoapplications at the pulmonary vein antrum using a 28-mm second-generation cryoballoon: a pilot study of extra-pulmonary vein ablation.

Isolation areas post-28-mm cryoballoon pulmonary vein isolation (CB-PVI) are smaller than post-radiofrequency PV antrum isolation at the left superior PV (LSPV) antrum and recurrent atrial fibrillation (AF) can originate from this area. This pilot study evaluated the impact of additional extra-PV CB applications at the LSPV antrum following conventional CB-PVI. Eighteen paroxysmal AF patients underwent CB-PVI with single 3-min freeze techniques. Following the CB-PVI, 2-min CB applications were added once or twice at the LSPV antrum. Before and after extra-PV ablation, left atrial (LA) 3-D electroanatomical maps were created. Seventy-two total PVs were successfully isolated with 4.2 ± 0.4 applications/patient with 28-mm CBs. The mean LA posterior wall (LAPW) and non-isolated LAPW areas were 14.9 ± 3.6 and 6.9 ± 2.8 cm2, respectively. After 1.6 ± 0.5 mean extra-PV applications, the upper non-isolated LAPW area significantly decreased from 3.3 ± 1.8 to 2.5 ± 1.8 cm2 (p < 0.001). The lowest esophageal temperatures during the extra-PV ablation were 27 °C. The total procedure and fluoroscopic times were 72.8 ± 13.1 and 15.2 ± 5.9 min, respectively. Silent gastric hypomotility was detected in 2/9 patients 1 day later, and mild PV stenosis was observed in 4/72 PVs 3 months later, but did not progress. At 12-month after single procedures, 16 (88.9%) patients were free from recurrent AF off antiarrhythmic drugs. A median of 8.0 [6.0-10.0] months later, PV reconnections were detected in 3/12 (25.0%) PVs. The non-isolated LAPW area was significantly larger in the chronic than acute phase (14.3 ± 5.2 cm2, p = 0.016). This pilot study suggested the potential feasibility of additional LSPV antral cryoapplications following a conventional CB-PVI. The strategy warrants further study in more patients.

Persistence of an iatrogenic atrial septal defect after a second-generation cryoballoon ablation of atrial fibrillation.

Persistent iatrogenic atrial septal defects (iASDs) can be observed after intervention requiring a left atria (LA) access, including pulmonary vein isolation (PVI) of atrial fibrillation (AF). We investigated the incidence of iASDs post-second-generation cryoballoon ablation and the pre-procedural predictors. Eighty-three paroxysmal AF patients underwent PVI using second-generation cryoballoons. The LA was accessed with single 15-Fr steerable sheaths following a radiofrequency transseptal puncture, and the iASD was evaluated with transthoracic echocardiography (TTE), a median of 9.3 (7.1-13.3) months post-procedure. All patients underwent pre-procedural contrast-enhanced multi-detector computed tomography (CT) to evaluate the LA and PV anatomy. iASDs were detected by TTE in 7 (8.4%) patients, a median of 15.5 (6.8-17.3) months post-procedure. Patients with iASDs had significantly larger LA volumes and smaller atrial septal angles, defined as the angle between the atrial septum and sagittal line on the horizontal section at the height of the fossa ovalis, which could be the transseptal puncture site measured on CT, and more likely hypertension than those without. Multivariate analyses revealed that the atrial septal angle was the sole predictor of iASDs [odds ratio 0.764, 95% confidence interval (CI) 0.624-0.935, p = 0.009], and the optimal cut-off value was 57.5° (sensitivity 85.7%, specificity 88.2%, 95% CI 0.873-0.995, p < 0.0001). Patients with iASDs were asymptomatic and had no adverse clinical events during a 17.7 (14.4-25.8) month median follow-up. iASDs were still detectable in 8.4% of patients a median of 15.5 months after the second-generation CB ablation, and the atrial septal angle might aid in predicting persistent iASDs.

Autonomic nervous system modulation and clinical outcome after pulmonary vein isolation using the second-generation cryoballoon.

BACKGROUND: The intrinsic cardiac autonomic nervous system (ANS) plays a significant role in atrial fibrillation (AF) mechanisms. This study evaluated the incidence and impact of intraprocedural vagal reactions and ANS modulation by pulmonary vein isolation (PVI) using second-generation cryoballoons on outcomes. METHODS: One hundred three paroxysmal AF patients underwent PVI with one 28-mm second-generation balloon. The median follow-up was 15.0 (12.0-18.0) months. ANS modulation was defined as a >20% cycle length decrease on 3-minute resting electrocardiograms at 1, 3, 6, and 12 months postindex procedure relative to baseline if sinus rhythm was maintained. RESULTS: Marked sinus arrests/bradycardia and atrioventricular block (intraprocedural vagal reaction) occurred in 14 and 2 patients, and all sinus arrest/bradycardia occurred in 44 patients with left superior pulmonary veins (PVs) targeted before right PVs. ANS modulation was identified in 66 of 95 (69.5%) patients, and it persisted 12-month postprocedure in 36 (37.9%) patients. Additional ß-blocker administration was required in 9 patients for sinus tachycardia. ANS modulation was similarly observed in patients with and without intraprocedural vagal reactions (P = 0.443). Forty-eight (46.6%) patients experienced early recurrences, and the single procedure success at 12 months was 72.7%. Neither intraprocedural vagal reactions nor ANS modulation predicted AF freedom within or after the blanking period. Thirty-three patients underwent second procedures, and reconnections were detected in 39 of 130 (30.0%) PVs among 23 (69.7%) patients. The incidence of reconnections was similar in patients with and without ANS modulation. CONCLUSIONS: Increased heart rate persisted in 37.9% of patients even at 12-month post-second-generation cryoballoon PVI. Neither intraprocedural vagal reactions nor increased heart rate predicted a single procedure clinical outcome.

Association Between Prior Aspirin Use and Morphological Features of Culprit Lesions at First Presentation of Acute Coronary Syndrome Assessed by Optical Coherence Tomography.

BACKGROUND: The effect of prior use of aspirin (ASA) on the onset of acute coronary syndrome (ACS) has not been clarified. This study used optical coherence tomography (OCT) to investigate the morphological features of culprit lesions of ACS in patients with prior ASA use.Methods and Results:In total, 442 patients with their first ACS episode undergoing OCT for the culprit lesions were investigated. Clinical characteristics, OCT findings, and adverse events at 30 days were compared between patients with prior ASA use and ASA-naïve patients (non-ASA). 67 patients (15.2%) had received ASA at presentation. The ASA group was older, had higher frequency of dyslipidemia and hypertension, and lower renal function than the non-ASA group. Non-ST-elevation ACS was more prevalent in the ASA than in the non-ASA group (79.1 vs. 53.6%, P<0.001). Propensity score matching yielded 49 patients in both groups. OCT revealed less frequent thrombi in the ASA than in the non-ASA group in both the entire (37.3 vs. 75.2%, P<0.001) and score-matched cohorts (38.8 vs. 75.5%, P<0.001), whereas no significant difference was observed in plaque characteristics. Rate of adverse events did not differ between the ASA and the non-ASA groups in the matched cohort. CONCLUSIONS: With a first ACS presentation, patients with prior ASA use were more likely to present with non-ST-elevation ACS with less frequent intraluminal thrombi, but no significant difference in underlying plaque characteristics or clinical course.

European Society of Cardiology (ESC) Annual Congress Report From Barcelona 2017.

From August 26th to 30th, the 2017 Annual Congress of the European Society of Cardiology (ESC 2017) was held in Barcelona, Spain. Despite the terrorism tradegy just before the ESC congress, the congress attracted many medical professionals from all over the world to discuss the recent topics in cardiovascular medicine in more than 500 sessions, including COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS Trial), CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), and ORION (which assessed the effect of a novel siRNA inhibitor to PCSK9 on reductions in low-density lipoprotein cholesterol). Japanese cardiologists and the Japanese Circulation Society greatly contributed to the congress. This report briefly introduces some late-breaking registry results, late-breaking clinical trials, and ESC Guidelines from the ESC 2017 Congress.

Beneficial Effects of Low-Intensity Pulsed Ultrasound Therapy on Right Ventricular Dysfunction in Animal Models.

Right ventricular failure (RVF) is a leading cause of death in patients with pulmonary hypertension; however, effective treatment remains to be developed. We have developed low-intensity pulsed ultrasound therapy for cardiovascular diseases. In this study, we demonstrated that the expression of endothelial nitric oxide synthase (eNOS) in RVF patients was downregulated and that eNOS expression and its downstream pathway were ameliorated through eNOS activation in 2 animal models of RVF. These results indicate that eNOS is an important therapeutic target of RVF, for which low-intensity pulsed ultrasound therapy is a promising therapy for patients with RVF.

Synthesis of [18F] fluorine-labeled K-2 derivatives as radiotracers for AMPA receptors.

INTRODUCTION: AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) receptors play a central role in neurotransmission and neuronal function. A positron emission tomography (PET) tracer for AMPA receptors, [11C]K-2, was recently developed by us to visualize AMPA receptors in the living human brain. [11C]K-2 is a derivative of 4-[2-(phenylsulphonylamino)ethylthio]-2,6-difuluoro-phenoxyacetamide (PEPA), and is labeled with the radioactive isotope 11C, which has a short half-life. PET drugs are usually labeled with 18F because of its long half-life. Therefore, we screened and identified potential 18F-labeled PET drugs for AMPA receptors (AMPA-PET drugs), which could provide an image equivalent to that of [11C]K-2. METHODS: Derivatives of K-2 labeled with 18F were synthesized and administered to rats and PET imaging was performed. The transferability of each compound to the brain and its correlation with the PET image of [11C]K-2 were evaluated from the obtained PET images. Furthermore, the specific binding ability of promising compounds to the AMPA receptor was evaluated by the PET imaging of rats, which we specifically knocked down the expression of AMPA by the lentivirus-mediated introduction of short hairpin RNA (shRNA) targeted to subunits of the AMPA receptor (GluA1-A3). The specific binding ability was also evaluated through electrophysiological experiments with acute brain slices. RESULTS: Some of the synthesized 18F-labeled candidate compounds showed a distribution similar to that of K-2, with reasonable transferability to the brain. In addition, from the evaluation of the specific binding ability to the AMPA receptor, a promising structure of an 18F-labeled AMPA PET drug was identified. This study also revealed that the alkylation of the sulfonamide group of PEPA enhances brain transferability.

Low-intensity pulsed ultrasound therapy promotes recovery from stroke by enhancing angio-neurogenesis in mice in vivo.

Since the treatment window of thrombolytic therapy for stroke is limited, new therapy remains to be developed. We have recently developed low-intensity pulsed ultrasound (LIPUS) therapy to improve cognitive dysfunction in mouse models of vascular dementia and Alzheimer's disease. Here, we further aimed to examine whether our LIPUS therapy improves neurological recovery from ischemic stroke, and if so, to elucidate the mechanisms involved. In a mouse model of middle cerebral artery occlusion (MCAO), we applied LIPUS (32 cycles, 193 mW/cm2) to the whole brain 3 times in the first week (days 1, 3, and 5) after MCAO. We evaluated neurological functions using behavioral tests and performed histological analyses. Furthermore, to elucidate how LIPUS works within the injured brain, we also tested the effects of LIPUS in endothelial nitric oxide synthase (eNOS)-deficient (eNOS-/-) mice. In wild-type mice, the LIPUS therapy markedly improved neurological functions in the tightrope and rotarod tests at 28 days after MCAO. Histological analyses showed that the LIPUS therapy significantly increased the numbers of CD31-positive blood vessels in the perifocal lesion and doublecortin (DCX)-positive neurons in the ischemic striatum, indicating the angio-neurogenesis effects of the therapy. Importantly, these beneficial effects of the LIPUS therapy were totally absent in eNOS-/- mice. No adverse effects of the LIPUS therapy were noted. These results indicate that the LIPUS therapy improves neurological functions after stroke through enhanced neuro-angiogenesis in mice in vivo in an eNOS-dependent manner, suggesting that it could a novel and non-invasive therapeutic option for stroke.

Low-intensity pulsed ultrasound ameliorates cardiac diastolic dysfunction in mice: a possible novel therapy for heart failure with preserved left ventricular ejection fraction.

AIMS: Heart failure with preserved left ventricular ejection fraction (HFpEF) is a serious health problem worldwide, as no effective therapy is yet available. We have previously demonstrated that our low-intensity pulsed ultrasound (LIPUS) therapy is effective and safe for angina and dementia. In this study, we aimed to examine whether the LIPUS therapy also ameliorates cardiac diastolic dysfunction in mice. METHODS AND RESULTS: Twelve-week-old obese diabetic mice (db/db) and their control littermates (db/+) were treated with either the LIPUS therapy [1.875 MHz, 32 cycles, Ispta (spatial peak temporal average intensity) 117-162 mW/cm2, 0.25 W/cm2] or placebo procedure two times a week for 4 weeks. At 20-week-old, transthoracic echocardiography and invasive haemodynamic analysis showed that cardiac diastolic function parameters, such as e', E/e', end-diastolic pressure-volume relationship, Tau, and dP/dt min, were all deteriorated in placebo-treated db/db mice compared with db/+ mice, while systolic function was preserved. Importantly, these cardiac diastolic function parameters were significantly ameliorated in the LIPUS-treated db/db mice. We also measured the force (F) and intracellular Ca2+ ([Ca2+]i) in trabeculae dissected from ventricles. We found that relaxation time and [Ca2+]i decay (Tau) were prolonged during electrically stimulated twitch contractions in db/db mice, both of which were significantly ameliorated in the LIPUS-treated db/db mice, indicating that the LIPUS therapy also improves relaxation properties at tissue level. Functionally, exercise capacity was also improved in the LIPUS-treated db/db mice. Histologically, db/db mice displayed progressed cardiomyocyte hypertrophy and myocardial interstitial fibrosis, while those changes were significantly suppressed in the LIPUS-treated db/db mice. Mechanistically, western blot showed that the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cGMP-protein kinase G (PKG) pathway and Ca2+-handling molecules were up-regulated in the LIPUS-treated heart. CONCLUSIONS: These results indicate that the LIPUS therapy ameliorates cardiac diastolic dysfunction in db/db mice through improvement of eNOS-NO-cGMP-PKG pathway and cardiomyocyte Ca2+-handling system, suggesting its potential usefulness for the treatment of HFpEF patients.

Impact of catheter ablation of atrial fibrillation on long-term clinical outcomes in patients with heart failure.

BACKGROUND: Heart failure (HF) promotes atrial fibrillation (AF) and AF worsens HF. This study aimed to investigate the long-term clinical outcomes after AF ablation in patients with HF. METHODS AND RESULTS: A total of 106 consecutive HF patients, including 51 (48.1%) with a reduced left ventricular ejection fraction (LVEF) (HFrEF) and 55 (51.9%) with a preserved LVEF (HFpEF), underwent AF ablation. All patients underwent successful pulmonary vein antrum isolation, and substrate modification was added in 38 (35.8%). The mean follow-up period was 32.4±18.6 months, and mean number of procedures was 1.4±0.5 per patient. Low-dose antiarrhythmic drugs were combined in 29 (27.3%) patients. Freedom from recurrent atrial arrhythmias (ATa), HF-related hospitalizations, and the composite endpoint (all-cause death, stroke, HF-related hospitalizations) at 3 years was 88.7%, 97.6%, and 97.6% in HFrEF patients, and 79.3%, 96.2%, and 91.8% in HFpEF patients, respectively. LVEF normalization (≥50%) was observed in 37 (72.5%) HFrEF patients post-ablation, and a smaller LV diastolic diameter (LVDd) was the sole predictor [odds ratio (OR)=0.863; 95% confidence interval (CI)=0.779-0.955, p=0.005]. Shortening of the LVDd (≥5mm) was observed in 16 (29.1%) HFpEF patients post-ablation, and no recurrence after the initial procedure was the sole predictor (OR=6.229; 95% CI=1.524-25.469, p=0.011). CONCLUSIONS: Catheter ablation of AF could be one of the important therapeutic options in the management of patients with HF combined with AF regardless of the type of HF.

Relationship between optical coherence tomography-defined in-stent neoatherosclerosis and out-stent arterial remodeling assessed by serial intravascular ultrasound examinations in late and very late drug-eluting stent failure.

BACKGROUND: Little is known regarding the association between chronological out-stent vessel remodeling and in-stent tissue characteristics of drug-eluting stent (DES) failure. We aimed to evaluate the relationship between serial vessel remodeling after DES implantation and neoatherosclerosis (NA) assessed by optical coherence tomography (OCT) in patients with DES failure. METHODS: Forty-eight patients with late and very late stent failure after DES implantation, who underwent intravascular ultrasound (IVUS) at both the initial percutaneous coronary intervention and the time of stent failure and OCT imaging at the time of stent failure, were retrospectively investigated. NA on OCT was defined as neointimal formation with the presence of lipids or calcification inside the stents. Lesions were divided into two groups: those with NA and those without NA (NA: n=21; non-NA: n=27). From the serial IVUS examinations, external elastic membrane (EEM) volume and out-stent plaque volume were normalized by stent length and their changes were compared between the two groups. RESULTS: The NA group showed older stent age [median, 5.1 years (IQR, 4.8-8.3) vs 1.4 years (IQR, 0.8-4.5); p<0.01] and more prevalent sirolimus-eluting stents (SES; 81.0% vs. 29.6%; p<0.01). IVUS findings of the NA group showed a greater serial increase in both normalized EEM volume and normalized out-stent plaque volume (OSPVI) [1.05 (0.41-1.90) vs. 0.11 (-0.64 to 0.80) mm2; p<0.01; and 0.88 (0.57-1.98) vs. 0.12 (-0.41 to 0.78) mm2; p<0.01]. On multivariate analysis, percentage change in OSPVI (OR, 1.07; 95% CI, 1.01-1.14; p=0.02) and SES (OR, 9.78; 95% CI, 2.20-43.40; p<0.01) remained independent predictors of NA. CONCLUSIONS: NA in late and very late DES failure was associated with out-stent positive vessel remodeling. In addition to SES, out-stent progressive positive remodeling may help predict NA in late and very late DES failure.

Low-energy cardiac shockwave therapy to suppress left ventricular remodeling in patients with acute myocardial infarction: a first-in-human study.

OBJECTIVE: Although primary percutaneous coronary intervention (PCI) substantially reduces the mortality of patients with acute myocardial infarction (AMI), left ventricular (LV) remodeling after AMI still remains an important issue in cardiovascular medicine. We have previously demonstrated that low-energy cardiac shockwave (SW) therapy ameliorates LV remodeling after AMI in pigs. In this first-in-human study, we examined the feasibility and the effects of the SW therapy on LV remodeling after AMI in humans. PATIENTS AND METHODS: Seventeen patients with AMI who successfully underwent primary PCI (peak-creatine kinase<4000 U/l) were treated with the SW therapy. Low-energy shock waves were applied to the ischemic border zone around the infarcted area at 2, 4, and 6 days since AMI. Next, we compared these patients with historical AMI controls by propensity score matching (N=25). RESULTS: There were no procedure-related complications or adverse effects. At 6 and 12 months after AMI, LV function as assessed by MRI showed no signs of deleterious LV remodeling. When we compared the SW-treated group with the historical AMI controls at 6 months after AMI, LV ejection fraction was significantly higher in the SW-treated group (N=7) than in the historical control group (N=25) by echocardiography (66±7 vs. 58±12%, P<0.05). LV end-diastolic dimension also tended to be smaller in the SW than in the control group (47.5±4.6 vs. 50.0±5.9 mm, P=0.29). CONCLUSION: These results suggest that low-energy extracorporeal cardiac SW therapy is feasible and may ameliorate postmyocardial infarction LV remodeling in patients with AMI as an adjunctive therapy to primary PCI.

Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia - Crucial roles of endothelial nitric oxide synthase.

BACKGROUND: Therapeutic focused-ultrasound to the hippocampus has been reported to exert neuroprotective effects on dementia. In the present study, we examined whether the whole-brain LIPUS (low-intensity pulsed ultrasound) therapy is effective and safe in 2 mouse models of dementia (vascular dementia, VaD and Alzheimer's disease, AD), and if so, to elucidate the common underlying mechanism(s) involved. METHODS: We used bilateral carotid artery stenosis (BCAS) model with micro-coils in male C57BL/6 mice as a VaD model and 5XFAD transgenic mice as an AD model. We applied the LIPUS therapy (1.875 MHz, 6.0 kHz, 32cycles) to the whole brain. RESULTS: In both models, the LIPUS therapy markedly ameliorated cognitive impairments (Y-maze test and/or passive avoidance test) associated with improved cerebral blood flow (CBF). Mechanistically, the LIPUS therapy significantly increased CD31-positive endothelial cells and Olig2-positive oligodendrocyte precursor cells (OPCs) in the VaD model, while it reduced Iba-1-positive microglias and amyloid-ß (Aß) plaque in the AD model. In both models, endothelium-related genes were significantly upregulated in RNA-sequencing, and expressions of endothelial nitric oxide synthase (eNOS) and neurotrophins were upregulated in Western blotting. Interestingly, the increases in glia cells and neurotrophin expressions showed significant correlations with eNOS expression. Importantly, these beneficial effects of LIPUS were absent in eNOS-knockout mice. CONCLUSIONS: These results indicate that the whole-brain LIPUS is an effective and non-invasive therapy for dementia by activating specific cells corresponding to each pathology, for which eNOS activation plays an important role as a common mechanism.

Electrical superior vena cava isolation using a novel pace-and-ablate technique under diaphragmatic electromyography monitoring.

BACKGROUND: Diaphragmatic compound motor action potential (CMAP) amplitude monitoring is a standard technique to anticipate phrenic nerve injury during cryoballoon ablation. OBJECTIVE: The purpose of this study was to evaluate the feasibility of a novel superior vena cava isolation (SVCI) technique using simultaneous pacing and ablation through the tip of a single mapping/ablation catheter. METHODS: Fifty-four patients with atrial fibrillation were included. Radiofrequency energy was delivered point by point uniformly for 20 seconds with a power of 20 W until achieving SVCI. Diaphragmatic CMAPs were obtained from modified surface electrodes by high-output pacing from the mapping/ablation catheter throughout the procedure (pace-and-ablate group). Applications were interrupted if CMAP amplitudes significantly decreased without fluoroscopy. The data were compared with those of the 54 patients undergoing conventional SVCI (conventional group). RESULTS: Successful SVCI procedures were achieved in all with a mean of 10.3 ± 2.9 applications. In total, among 559 ablation sites, CMAPs were recorded at 95 (17.0%) with baseline amplitudes of 0.45 ± 0.23 mV. In 10 patients (18.5%), isolation was achieved without any radiofrequency deliveries at CMAP-recorded sites. Among the 95 applications, 6 (6.3%) were interrupted because of CMAP amplitude reductions. At the remaining 88 sites, 20-second radiofrequency applications were delivered without any amplitude decrease (from 0.45 ± 0.21 to 0.46 ± 0.23 mV; P = .885). Phrenic nerve injury occurred in 1 patient in the pace-and-ablate group, which recovered 3 months later, and in 3 conventional group patients, of whom 1 recovered 1 month later (P = .308). The total procedure time tended to be shorter (14.5 ± 6.3 minutes vs 16.7 ± 9.2 minutes; P = .153) and fluoroscopy time significantly shorter (3.9 ± 3.0 minutes vs 6.7 ± 5.7 minutes, P = .002) in the pace-and-ablate group than in the conventional group. CONCLUSION: A novel and simple pace-and-ablate technique under diaphragmatic electromyography monitoring might be feasible for an electrical SVCI.

Thromboembolic Risks of the Procedural Process in Second-Generation Cryoballoon Ablation Procedures: Analysis From Real-Time Transcranial Doppler Monitoring.

BACKGROUND: Atrial fibrillation ablation is associated with substantial risks of silent cerebral events (SCEs) or silent cerebral lesions. We investigated which procedural processes during cryoballoon procedures carried a risk. METHODS AND RESULTS: Forty paroxysmal atrial fibrillation patients underwent pulmonary vein isolation using second-generation cryoballoons with single 28-mm balloon 3-minute freeze techniques. Microembolic signals (MESs) were monitored by transcranial Doppler throughout all procedures. Brain magnetic resonance imaging was obtained pre- and post-procedure in 34 patients (85.0%). Of 158 pulmonary veins, 152 (96.2%) were isolated using cryoablation, and 6 required touch-up radiofrequency ablation. A mean of 5.0±1.2 cryoballoon applications was applied, and the left atrial dwell time was 76.7±22.4 minutes. The total MES counts/procedures were 522 (426-626). Left atrial access and Flexcath sheath insertion generated 25 (11-44) and 34 (24-53) MESs. Using radiofrequency ablation for transseptal access increased the MES count during transseptal punctures. During cryoapplications, MES counts were greatest during first applications (117 [81-157]), especially after balloon stretch/deflations (43 [21-81]). Pre- and post-pulmonary vein potential mapping with Lasso catheters generated 57 (21-88) and 61 (36-88) MESs. Reinsertion of once withdrawn cryoballoons and subsequent applications produced 205 (156-310) MESs. Touch-up ablation generated 32 (19-62) MESs, whereas electric cardioversion generated no MESs. SCEs and silent cerebral lesions were detected in 11 (32.3%) and 4 (11.7%) patients, respectively. The patients with SCEs were older than those without; however, there were no significant factors associated with SCEs. CONCLUSIONS: A significant number of MESs and SCE/silent cerebral lesion occurrences were observed during second-generation cryoballoon ablation procedures. MESs were recorded during a variety of steps throughout the procedure; however, the majority occurred during phases with a high probability of gaseous emboli.

Peeled Guidewire Coating with Debulked Plaque Obtained by Directional Coronary Atherectomy.

Percutaneous directional coronary atherectomy (DCA) is a plaque debulking method performed in Japan, and recently a renewed DCA device has been launched. We present a case with a tight left anterior descending lesion undergoing percutaneous coronary intervention with application of DCA. After several sessions of DCA, white plaques accompanied by green, stringed materials were obtained from the device; some materials were considerably long (approximately 15 mm in length). A drug-eluting stent was subsequently implanted, and the procedure was completed successfully without any complications. The extracted plaques and artificial materials were pathologically examined, and no inflammatory changes were detected on plaques adjacent to the material. Assessing pathological findings and structure of the DCA catheter, the obtained artificial materials were considered as peeled guidewire, possibly resulting from the friction between the guidewire and metallic bearing in the housing of DCA catheter. Of note, this phenomenon has been recognized even in other DCA cases in which guidewires of the other kind are used. We report this phenomenon for the first time, warning of theoretically possible distal embolization of artificial materials caused by any debulking devices.

Predictors and clinical implication of high-sensitivity cardiac troponin-I elevation following diagnostic cardiac catheterisations.

OBJECTIVES: Although diagnostic coronary angiography (CAG) is performed worldwide, procedure-related myocardial necrosis (PMN) following diagnostic catheter-based procedures has not been well investigated. The aim of this study was to determine clinical and procedural factors associated with PMN, using a high-sensitivity cardiac troponin I (hs-cTnI) assay, and to investigate the clinical implications of PMN. METHODS: Among 697 patients undergoing elective CAG and pre- and post-procedural hs-cTnI (pre-TnI, post-TnI, respectively) measurements, a total of 538 patients (124 female) were evaluated, with 2.2% lost during follow-up. Minor PMN was defined as post-TnI above the sex-specific upper reference limit (URL), with a 20% increase from the pre-TnI level. Major PMN was defined as post-TnI above 5x the URL. Clinical and procedural factors predicting PMN and the association between PMN and major adverse cardiac events (MACE) following CAG were examined. RESULTS: PMN of any type was detected in 178 patients (33.0%), while major PMN was observed in 32 patients (5.9%). Female sex, estimated glomerular filtration rate, procedural time, left ventricular end-diastolic pressure (LVEDP) and fractional flow reserve measurement independently predicted any PMN; whereas, only LVEDP and log-transformed N-terminal pro-brain natriuretic peptide independently predicted major PMN. The incidence of MACE was significantly associated with major PMN. Cox proportional-hazards models revealed that major PMN, pre-TnI, and the absence of statin use were independently associated with MACE. CONCLUSIONS: Diagnostic cardiac catheteriation may highlight cardiomyocyte susceptibility to stress in patients with or without CAD. CAG-related major myocardial injury might be associated with future adverse cardiac events independently of the presence or absence of functional stenosis.

Guidewire shadow artifacts in optical coherence tomography.

BACKGROUND: Because of the high resolution made possible by optical coherence tomography (OCT), previously indistinguishable guidewire artifacts are recognized during coronary imaging, and these affect image interpretation. This study aimed to assess the effect of guidewire size and structure on the artifacts produced and to introduce a novel guidewire specifically for OCT imaging that produces fewer artifacts. Elimination or minimization of guidewire artifacts supports optimal OCT imaging. METHODS: Silicon tubes simulating the coronary arteries were used to assess guidewire shadow artifacts in OCT imaging. The angles of artifacts produced by 4 types of guidewires were evaluated, including our newly designed guidewire. Clinical data of guidewire artifacts were also obtained from 20 patients with coronary artery disease who underwent OCT examination with these guidewires before stenting. RESULTS: The angles of the guidewire artifacts decreased with a reduction in the wire diameter. Wires with the dipping polymer structure produced unique artifacts brought about by a combination of the sparse spring coil structure, wire core, and polymer, and these affected image interpretation. The guidewire designed in this study could be used in clinical settings and produced fewer artifacts than the other examined guidewires. Our novel guidewire, which had a small diameter, lacked the dipping polymer structure, and was easy to handle, was successfully used for OCT imaging. CONCLUSIONS: Guidewire artifacts are affected by guidewire size and structure. We developed a specialized guidewire for optimal OCT imaging that effectively produced fewer shadow artifacts than its generally used counterparts.