Comprehensive clinical outcomes of drug-coated balloon treatment for coronary artery disease. Insights from a single-center experience.

BACKGROUND: Some clinical trials have verified the efficacy and safety of paclitaxel drug-coated balloon (DCB) for small vessel coronary artery disease. However, nonsmall vessel and calcified lesions received less attention. AIMS: This study aimed to investigate the efficacy of DCB treatment for various types of coronary artery lesions, including not only small vessel disease but also nonsmall vessel disease and calcified lesions. In this real-world clinical practice study, in-stent restenosis was excluded. METHODS: This study consecutively included 934 patients with 1751 nonstented lesions who received DCB at a cardiovascular center in Kyoto Katsura Hospital in Japan between 2009 and 2012 and 2014 to 2019. This study enrolled and retrospectively analyzed all of the patients. Eligible patients routinely underwent follow-up angiography at 6-8 months after percutaneous coronary intervention. The primary endpoint includes target lesion revascularization (TLR) during follow-up. Further, this study calculated the predictor of TLR using multivariate analysis. RESULTS: This study included the lesions involving 46.4% of type B2/C, 26.9% with severe calcification, and 6.0% with DCB restenosis. Mean DCB diameter and length were 2.75 ± 0.51 mm and 24.2 ± 9.6 mm, respectively. The median follow-up duration was 18 months. Follow-up angiography revealed a TLR rate of 9% and a restenosis rate of 9%. This study identified hemodialysis and current smoking as independent TLR predictors. CONCLUSION: In routine clinical practice, the effectiveness of DCB was observed consistently across various types of coronary artery disease.

A dominant STIM1 mutation causes Stormorken syndrome.

Stormorken syndrome is a rare autosomal-dominant disease with mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis. A heterozygous missense mutation in STIM1 exon 7 (c.910C>T; p.Arg304Trp) (NM_003156.3) was found to segregate with the disease in six Stormorken syndrome patients in four families. Upon sensing Ca(2+) depletion in the endoplasmic reticulum lumen, STIM1 undergoes a conformational change enabling it to interact with and open ORAI1, a Ca(2+) release-activated Ca(2+) channel located in the plasma membrane. The STIM1 mutation found in Stormorken syndrome patients is located in the coiled-coil 1 domain, which might play a role in keeping STIM1 inactive. In agreement with a possible gain-of-function mutation in STIM1, blood platelets from patients were in a preactivated state with high exposure of aminophospholipids on the outer surface of the plasma membrane. Resting Ca(2+) levels were elevated in platelets from the patients compared with controls, and store-operated Ca(2+) entry was markedly attenuated, further supporting constitutive activity of STIM1 and ORAI1. Thus, our data are compatible with a near-maximal activation of STIM1 in Stormorken syndrome patients. We conclude that the heterozygous mutation c.910C>T causes the complex phenotype that defines this syndrome.

Acute and mid-term results of percutaneous coronary intervention for severely calcified coronary artery lesions with orbital atherectomy system.

OBJECTIVES: Severely calcified lesions present many challenges for percutaneous coronary intervention (PCI). This study aimed to assess the safety and efficacy of the orbital atherectomy system (OAS) in treating calcified coronary lesions. METHODS: The present study included 422 consecutive cases (546 lesions) who underwent PCI with OAS in Kyoto Katsura Hospital from February 2018 to December 2021. We assessed the following clinical outcomes after OAS was used for severely calcified lesions: procedure success, angiographic complications, in-hospital Major Adverse Cardiovascular Events (MACE), and mid-term results. The primary endpoint was the combination of incidence of MACE at 12 months, cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR). RESULTS: Of all the cases, 74% patients were men and the mean age was 76.5 years. In total, 81% of lesions were treated with drug-coated balloon, and 14% were implanted with stents. Procedural success rate was 96.3%. Coronary perforation occurred in 0.5% and persistent slow flow in 2% lesions. There was 1 cardiac death (0.5%), 43 periprocedural MIs (10.2%), and no TLR as in-hospital MACE. The incidence of MACE at 12 months was 8.4%, including 2.1% cardiac death and 6.9% TLR. In multivariate analysis, CKD, hemodialysis, and restenosis lesions were independently associated with MACE at 12 months. Periprocedural MI was not an independent predictor of MACE. CONCLUSIONS: This study suggested that OAS is a safe and effective treatment option for calcified coronary lesions with acceptable acute and mid-term results; thus, it can be an alternate for reducing calcified plaque.

Intravenous perampanel as an alternative to the oral formulations in Japanese patients with epilepsy.

OBJECTIVE: Perampanel is an oral anti-seizure medication, which is approved in Japan for focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, as monotherapy/adjunctive therapy in patients aged 4 years and older. Treatment for generalized tonic-clonic seizures as adjunctive therapy in patients aged 12 years and older is approved as well. We evaluated the feasibility of intravenous (IV) administration of perampanel as an alternative to oral administration. METHODS: Study 240 (NCT03754582) was an uncontrolled, open-label study of IV perampanel, conducted in 21 Japanese patients with epilepsy who received a stable dose of 8-12 mg/day of oral perampanel. Patients received 30-minute IV infusions at equivalent daily doses of oral perampanel for 4 days, then were switched back to oral perampanel. Safety, tolerability, plasma concentration, and maintenance of efficacy throughout the transition between IV and oral dosing of perampanel were assessed. As supportive data, a subgroup analysis was also conducted using data from healthy Japanese subjects (n = 18) who were enrolled in Study 050 (NCT03376997) investigating the pharmacokinetics and safety of IV perampanel in healthy subjects who received an IV infusion (30-, 60-, or 90-minute) of perampanel 12 mg and a single oral administration of perampanel 12-mg tablet. RESULTS: In Study 240, the transition between 30-minute IV and oral perampanel dosing was associated with a ≤1.4-fold increase in the mean change in maximum observed concentration of perampanel. Seizure outcomes demonstrated no considerable changes in efficacy before, during, or after 30-minute IV dosing of perampanel. The safety profiles were similar between IV and oral formulations. In Study 050, the pharmacokinetics of 30- or 60-minute IV infusion of perampanel further support the interchangeability between oral and IV formulations in the Japanese subjects. SIGNIFICANCE: These results support that 30-minute IV perampanel may be a potential short-term alternative to oral formulations for patients with epilepsy.

A high dose of dexmedetomidine using the BIS monitor™ for diagnostic and interventional cardiac catheterization in a toddler with congenital heart disease.

Dexmedetomidine (DEX) for sedation in diagnostic and interventional cardiac catheterization (DICC) has been reported to require other drugs or rescue drugs because of its insufficient sedative effect when used alone. We administered DEX and adjusted its dose according to the bispectral index (BIS) monitor™ for DICC in a toddler; consequently, a high dose of DEX had to be administered. The patient was a 1-year and 4-month-old boy who was scheduled to undergo DICC after intracardiac repair. We used DEX alone as the sedative because this was expected to avoid oxygen supply and mechanical ventilation and to produce a safe situation for procedures around the neck. DEX was administered at the dose of 1-15 µg/kg/h according to BIS monitor™; administration of cardiovascular drugs or oxygen supply or assist ventilation, except chin lift, were not needed. The maximum predicted plasma concentration (pCp) of DEX and mean pCp were calculated as 6.1 and 4.1 ng/mL, respectively. A high dose of DEX may be required for DICC sedation, as for MRI sedation, in many cases. Although further studies should be conducted to reveal the merits and demerits of DEX in cardiac catheterization, a high dose of DEX may be useful in some cases.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

BACKGROUND AND OBJECTIVES: The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. METHODS: This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. RESULTS: A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). DISCUSSION: One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

Interictal epileptiform discharges as a predictive biomarker for recurrence of poststroke epilepsy.

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Antiseizure medications for post-stroke epilepsy: A real-world prospective cohort study.

BACKGROUND AND PURPOSE: The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE. METHODS: This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens. RESULTS: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001). CONCLUSIONS: Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.

An unmappable ventricular tachycardia in the arrhythmogenic right ventricular cardiomyopathy: elucidation of critical isolated delayed components with high-resolution electroanatomical mapping.

Unmappable ventricular tachycardia (VT) is a challenge in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). We report a feasible strategy for a curative ablation. In the present case with ARVC, the clinical VT showed a single morphology of left bundle branch block with inferior axis. Neither activation mapping nor entrainment mapping could be done because of instability of the haemodynamics. Furthermore, pace mapping could not be obtained due to electrically unexcitable scars covering with the RV. We found isolated delayed components (IDCs) in the diastolic phase recorded within the scar areas. Electroanatomical mapping (CARTO) with tiered decreasing voltage definition revealed that IDCs were delineated on the narrow conducting channels along or between the complete scars (amplitude < or =0.1 mV). Isolated delayed components on the narrow channels were targeted under the guidance with CARTO. After 11 radiofrequency applications, the clinical VT was eliminated. Moreover, epsilon waves recorded on the 12-lead electrocardiogram disappeared. No ventricular tachyarrhythmia was recognized at 6-month follow-up. Isolated delayed component ablation with high-resolution CARTO map was feasible and provided a curative approach in the treatment of an unmappable VT in ARVC.

Ventricular late potential in patients with apparently normal electrocardiogram; predictor of Brugada syndrome.

BACKGROUND: Brugada syndrome can be overlooked due to its dynamic change in its electrocardiogram (ECG) manifestation. We hypothesized that positive ventricular late potential (VLP) in patients with nonspecific ECG would predict the inducible coved ST elevation (type-1 Brugada ECG) and the patients at high risk. METHODS: Thirty-four patients of nonspecific ECG without structural heart disease were eligible for this study. All patients were referred for evaluation of syncopal episodes and/or cardiac arrest and/or frequent episodes of ventricular premature contractions. We assessed the correlation between baseline VLP and the alteration to a drug-induced type-1 Brugada ECG, and also evaluated the diagnostic accuracy of positive VLP in normal ECG subjects for the appearance of a drug-induced type-1 Brugada ECG. RESULTS: Twenty-one patients presented positive VLP and 13 patients showed negative VLP. Parameters of VLP (fQRSd, RMS(40), LAS(40)) presented significant correlation with the alteration to a type-1 ECG by pilsicainide. VLP demonstrated high sensitivity and negative predictive value for the prediction of type-1 Brugada ECG. Furthermore, in their follow-up, at least two cases of ventricular fibrillation were recognized in 21 of positive VLP patients with apparently normal ECGs. CONCLUSIONS: VLP in apparently normal ECG can predict the alteration to a drug-induced type-1 Brugada ECG and unmask the patients at risk.

Acute and mid-term outcomes of drug-coated balloon following rotational atherectomy.

Rotational atherectomy (RA) is effective for reducing calcified plaque volume as part of percutaneous coronary intervention (PCI). Most lesions are then treated by stenting, but we often observe in-stent restenosis (ISR) due to an under-expanded stent associated with severe calcification, a condition that is particularly challenging to treat. It is unknown if drug-coated balloon (DCB) application following RA can be used as a "stentless" treatment strategy for calcified lesions. The aim of this study is to assess the acute and mid-term efficacy of DCB following RA (RA + DCB) at our institute and to evaluate the overall clinical utility of this stentless strategy for complex calcified lesions. From October 2014 to June 2018, 3644 lesions in 2424 consecutive cases were treated with PCI at our institute. Rotational atherectomy was used for 12.3% of all lesions and 42.3% of these RA-treated lesions were then treated using DCBs (n = 190 RA + DCB-treated lesions, of which 72% were in males). In-hospital major adverse cardiac events included only one case of non-Q-wave myocardial infarction. Average duration of follow-up coronary angiography after initial PCI was 199 ± 61 days. Angiographic restenosis was observed in 17.8% of RA + DCB-treated lesions, with mean late lumen loss of 0.23 ± 0.69 mm, while late lumen enlargement was observed in 39.1% of RA + DCB-treated lesions. At mid-term clinical follow-up, there were no cardiac deaths and target lesion revascularization rate was only 16.4%. Rotational atherectomy followed by DCB demonstrated acceptable acute and mid-term efficacy, suggesting that this stentless strategy may be an effective option for complex calcified lesions with high risk of ISR.

STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone.

Calcium signaling plays a central role in bone development and homeostasis. Store operated calcium entry (SOCE) is an important calcium influx pathway mediated by calcium release activated calcium (CRAC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensing protein important for SOCE. We generated a mouse model expressing the STIM1 R304W mutation, causing Stormorken syndrome in humans. Stim1R304W/R304W mice showed perinatal lethality, and the only three animals that survived into adulthood presented with reduced growth, low body weight, and thoracic kyphosis. Radiographs revealed a reduced number of ribs in the Stim1R304W/R304W mice. Microcomputed tomography data revealed decreased cortical bone thickness and increased trabecular bone volume fraction in Stim1R304W/R304W mice, which had thinner and more compact bone compared to wild type mice. The Stim1R304W/+ mice showed an intermediate phenotype. Histological analyses showed that the Stim1R304W/R304W mice had abnormal bone architecture, with markedly increased number of trabeculae and reduced bone marrow cavity. Homozygous mice showed STIM1 positive osteocytes and osteoblasts. These findings highlight the critical role of the gain-of-function (GoF) STIM1 R304W protein in skeletal development and homeostasis in mice. Furthermore, the novel feature of bilateral subgingival hair growth on the lower incisors in the Stim1R304W/R304W mice and 25 % of the heterozygous mice indicate that the GoF STIM1 R304W protein also induces an abnormal epithelial cell fate.

Contribution of subtraction ictal SPECT coregistered to MRI to epilepsy surgery: a multicenter study.

OBJECTIVE: A multicenter prospective study was performed to assess the additional value of a subtraction ictal SPECT coregistered to MRI (SISCOM) technique to traditional side-by-side comparison of ictal- and interictal SPECT images in epilepsy surgery. METHODS: One hundred and twenty-three patients with temporal and extratemporal lobe epilepsy who had undergone epilepsy surgery after evaluation of scalp ictal and interictal electroencephalogram (EEG), MRI, and ictal and interictal SPECT scans were followed up in terms of postsurgical outcome for a period of at least 1 year. Three reviewers localized the epileptogenic focus using ictal and interictal SPECT images first by side-by-side comparison and subsequently by SISCOM. Concordance of the localization of the epileptogenic focus by SPECT diagnosis with the surgical site and inter-observer agreement between reviewers was compared between side-by-side comparison and SISCOM. Logistic regression analysis was performed in predicting the surgical outcome with the dependent variable being the achievement of a good postsurgical outcome and the independent variables using the SISCOM, side-by-side comparison of ictal and interictal SPECT images, MRI, and scalp ictal EEG. RESULTS: The SISCOM presented better concordance in extratemporal lobe epilepsy and less concordance in temporal lobe epilepsy than side-by-side comparison. Inter-observer concordance was higher in SISCOM than in side-by-side comparison. Much higher concordance of the epileptogenic focus by SPECT diagnosis with the surgical site was obtained in patients with good surgical outcome than in those with poor surgical outcome. These differences in concordance between good and poor surgical outcomes were greater in SISCOM than in side-by-side comparison. Logistic regression analysis showed the highest odds ratio of 12.391 (95% confidence interval; 3.319, 46.254) by SISCOM evaluation for concordance of the epileptogenic focus with the surgical site in predicting good surgical outcome. CONCLUSIONS: A SISCOM technique of ictal and interictal SPECT images provides higher predictive value of good surgical outcome and more reliability on the diagnosis of the epileptogenic focus than side-by-side comparison in medically intractable partial epilepsy.

How minimally interrupted direct oral anticoagulants affect intraprocedural anticoagulation during atrial fibrillation ablation? Insights from a Japanese single-center retrospective study.

BACKGROUND: Data are still lacking regarding the effects of minimally interrupted direct oral anticoagulants (MID) on the intensity of intraprocedural anticoagulation of atrial fibrillation (AF) ablation. METHODS: A total of consecutive 269 patients who undergone AF ablation were eligible for the study. All oral anticoagulants (OACs) were discontinued just one dose before the procedure except warfarin. We assessed the total required dose of UFH and time-to-target ACT > 300 seconds (TTA) for each of direct oral anticoagulant (DOAC) groups compared with the uninterrupted warfarin group. RESULTS: DOACs were used in 86% of the patients in the present study (dabigatran group (DG)-17%, rivaroxaban group (RG)-30%, apixaban group (AG)-29%, and edoxaban group (EG)-10%). DG and EG used comparable dose of total UFH to WG (WG vs DG; 206 ± 53 U/kg vs 231 ± 63 U/kg; P = .664, vs EG; 239 ± 67 U/kg; P = .335), while RG and AG required higher total UFH (WG vs RG; 206 ± 53 U/kg vs 270 ± 63 U/kg; P < .001, vs AG; 263 ± 62 U/kg; P < .001). TTA was significantly longer in RG (RG:73 ± 28 minutes vs WG:51 ± 25 minutes; P = .001), AG (AG:64 ± 26 minutes vs WG:51 ± 25 minutes; P = .02), and EG (EG:67 ± 34 minutes vs WG:51 ± 25 minutes; P = .02) than WG, whereas DG was comparable to WG (DG:51 ± 29 minutes vs WG:51 ± 25 minutes; P = NS). Especially, only RG demonstrated significantly slower increase in ACT than WG (P = .013). In the multivariate analysis, warfarin or dabigatran use, age > 75 years, and body weight < 60 kg are clinical predictors for achieving TTA within 60 minutes (TTA-60). CONCLUSION: MID-dabigatran was comparable to uninterrupted warfarin, whereas MID-factor Xa inhibitors were not. MID is a feasible protocol; however, we should be aware of its effect on the intraprocedural anticoagulation and differences among DOACs in the responsiveness to heparin.

Clinical and angiographic outcomes of coronary dissection after paclitaxel-coated balloon angioplasty for small vessel coronary artery disease.

The mechanism of how angiographic results following paclitaxel-coated balloon (PCB) treatment for small vessel disease affect patient outcome remains unknown. In the present study, we aimed to investigate the correlation between coronary dissection immediately after PCB angioplasty and midterm outcome. From March 2014 to March 2017, 171 consecutive patients with 228 native coronary artery lesions who received PCB angioplasty at a single center were enrolled retrospectively. Lesions with a reference vessel diameter > 2.8 mm were excluded. There were dissections in 80% of the lesions immediately following PCB angioplasty. Of these, 38% were type A, 29% were type B, and 13% were type C or more severe dissection. No patient required revascularization during hospitalization. We were able to follow 159 patients (212 lesions) clinically for > 6 months, from among whom target lesion revascularization (TLR) was performed in 7% of the patients. Follow-up angiography was performed on 143 lesions (67%), and complete healing of all dissections was noted. The rates of restenosis and late lumen enlargement were 12% and 56%, respectively. Multivariate analysis identified that a bending lesion was an independent predictor of TLR, and type C-E dissection and imaging device use were independent predictors of restenosis. Conversely, lesions with type B dissection had a larger net gain than lesions with type A or no dissection. Leaving the dissection uncovered after PCB angioplasty seems to be safe, resulting in a low acute event rate. The type B dissection after PCB angioplasty was the most therapeutic dissection.

Novel pathogenic VPS13A gene mutations in Japanese patients with chorea-acanthocytosis.

OBJECTIVE: To identify mutations in vacuolar protein sorting 13A (VPS13A) for Japanese patients with suspected chorea-acanthocytosis (ChAc). METHODS: We performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis of the VPS13A gene, and chorein Western blotting of erythrocyte ghosts. As the results of the analysis, 17 patients were molecularly diagnosed with ChAc. In addition, we investigated the distribution of VPS13A gene mutations and clinical symptoms in a total of 39 molecularly diagnosed Japanese patients with ChAc, including 22 previously reported cases. RESULTS: We identified 11 novel pathogenic mutations, including 1 novel CNV. Excluding 5 patients with the unknown symptoms, 97.1% of patients displayed various neuropsychiatric symptoms or forms of cognitive dysfunction during the course of disease. The patients carrying the 2 major mutations representing over half of the mutations, exon 60-61 deletion and exon 37 c.4411C>T (R1471X), were localized in western Japan. CONCLUSIONS: We identified 13 different mutations in VPS13A, including 11 novel mutations, and verified the clinical manifestations in 39 Japanese patients with ChAc.

Nifekalant and disopyramide in a patient with short QT syndrome: evaluation of pharmacological effects and electrophysiological properties.

We assessed several pharmacological effects on electrocardiogram parameters and effective refractory period (ERP) in a patient with a short QT syndrome (SQTS). Pharmacological challenge tests revealed that disopyramide and selective I(kr) blocker, nifekalant normalized QT interval, and ERP of the atrial and ventricular myocardium. This study suggested that disopyramide and nifekalant should be feasible for the drug treatment of the SQTS. Moreover, QT interval was paradoxically prolonged at higher heart rates induced with isoproterenol infusion or an exercise test, although the mechanism of this QT prolongation remains to be investigated.

Correlation between periodic sharp wave complexes and diffusion-weighted magnetic resonance images in early stage of Creutzfeldt-Jakob disease: a report of two cases.

We evaluated the correlation between the periodic sharp wave complexes (PSWC) on EEG and the spreading lesions on diffusion-weighted (DW) magnetic resonance images (MRI) in two cases of Creutzfeldt-Jakob disease (CJD). In Case 1, DW-MRI showed increased signal intensity in bilateral caudate, bilateral parietal, and right temporo-occipital cortex at 7 weeks after onset. EEG showed PSWC of 1Hz frequency at 8 weeks after onset. Source localization analysis of the PSWC was conducted by low resolution electromagnetic tomography (LORETA), and localized the source in the cortex of bilateral parietal lobes and mesial frontal lobe, predominantly on the right side. At 10 weeks after onset, the PSWC source spread to bilateral parietal and frontal lobes, and the same spread was also observed for the lesion depicted on DW-MRI. In Case 2, DW images showed high signal intensity in the right parietal cortical lesion at 4 weeks after onset. PSWC of 2Hz frequency were seen in the routine EEG, and the source was localized in bilateral frontal lobes and right parietal lobe at 7 weeks after onset. The lesions on DW images also spread to bilateral frontal and parietal lobes. Nine weeks after onset, the source of PSWC extended to the right frontal lobe and bilateral parietal lobes, while the lesions on DW images progressed to the right temporal lobe and bilateral fronto-parieto-occipital lobes. Spreading DW-MRI lesions may correlate with the appearance of PSWC.