Reduction of thromboembolic complications during the endovascular treatment of unruptured aneurysms by employing a tailored dual antiplatelet regimen using aspirin and prasugrel.

BACKGROUND: Thromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel. METHODS: Patients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU <240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint. RESULTS: The tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group. CONCLUSION: The results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications.

Delayed Hemiparkinsonism Associated with Kernohan's Notch in a Patient with a Ruptured Arteriovenous Malformation.

A 24-year-old female patient was admitted for a right frontal intracranial hematoma with an uncal herniation due to a ruptured arteriovenous malformation and therefore underwent emergency surgery. Neuroimaging revealed left-sided midbrain notching against the tentorium, indicating Kernohan's notch phenomenon. She denied experiencing any short-term neurological deficits but right-sided delayed hemiparkinsonism developed 18 months later. Dopamine transporter tracer uptake was severely reduced in the left striatum, suggesting nigrostriatal degeneration secondary to Kernohan's notch. Uncal herniations are potentially fatal, but surgery can save the patient's life and improve the functional outcomes. Clinicians should therefore be aware of delayed hemiparkinsonism as a rare complication of Kernohan's notch phenomenon.

Idiopathic middle meningeal artery and middle meningeal vein fistula presenting as temporal intraparenchymal hemorrhage.

Middle meningeal artery (MMA) and middle meningeal vein (MMV) fistula is a rare lesion. Hemorrhagic propensity for this pathology has not been widely recognized. We encountered a case of idiopathic MMA-MMV fistula presenting as intracerebral hemorrhage. MMA and MMV showed a single fistula and the enlarged MMV coiled around the MMA, resembling a varix. We treated the case using endovascular techniques. This case highlights the anatomy along the course of the MMV and is unique, since no backward leptomeningeal drainage was observed. A bone defect in the meningeal groove on computed tomography and a "green caviar appearance" on angiography may be characteristic of this rare pathology.

Initial Report of the Perioperative Platelet Aggregation Test Using Hematracer ZEN in Neuroendovascular Therapy.

Objective: We report the characteristics of the platelet aggregation test using Hematracer ZEN (HTZ; DS medical, Tokyo, Japan) during the perioperative period. Methods: Among patients undergoing neuroendovascular treatment (EVT) at our hospital between June 2019 and June 2020, 42 consecutive patients with preoperative dual antiplatelet therapy (DAPT) were included. Oral administration of aspirin (ASA) at 81 mg and clopidogrel (CLP) at 75 mg was started 7 days before treatment (Flow Diverter [FD]: 14 days before). We evaluated platelet aggregation activity the day before treatment (FD: 2 days before) using HTZ. We adjusted the CLP dose according to the platelet aggregation test in each patient. We evaluated the platelet aggregating activity after EVT in patients requiring an intracranial stent or in which CLP was adjusted before EVT. Results: Platelet aggregating activity was able to be evaluated in all patients. In the preoperative examination, the efficacy of CLP was insufficient in one patient (2.4%), optimal medical effects were confirmed in 16 (38.1%), mildly excessive effects were noted in 10 (23.8%), and highly excessive effects were noted in 15 (35.7%). Reassessment was performed postoperatively in 20 patients. We switched CLP to prasugrel in one patient in which the CLP efficacy was considered insufficient in the preoperative evaluation. We reduced the CLP dose in seven patients with marked overdose, and the optimum range was reached in all. We did not adjust the CLP dose in 12 patients judged to have optimal or mildly excessive effects preoperatively, but 4 exhibited highly excessive drug efficacy and required CLP reduction. No postoperative symptomatic cerebral infarction or intracranial hemorrhage was observed (mean observation period: 11 months, range: 4-16 months). Conclusion: The platelet aggregation test using HTZ was simple and inexpensive, and was useful for adjusting the dose of antiplatelet drugs, but its utility should be evaluated in more patients.

Carotid Endarterectomy for Intractable Repetitive Stenosis Following Carotid Artery Stenting.

BACKGROUND: Restenosis after carotid artery stenting has raised concerns regarding the long-term durability of carotid stenting. Recurrent restenosis after multiple endovascular interventions may pose a challenge for clinicians. CASE DESCRIPTION: We encountered 2 cases of intractable restenosis after redo-carotid artery stenting and performed carotid endarterectomy. We removed the embedded stent and plaque simultaneously, used the internal shunting system, and performed patch angioplasty with no further recurrence. CONCLUSION: Carotid endarterectomy could be considered as a first-line treatment for recurrent stenosis that proves refractory to multiple endovascular interventions.

Cortical Blood Flow Insufficiency Scores with Computed Tomography Perfusion can Predict Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients: A Cohort Study.

BACKGROUND: The World Federation of Neurosurgical Societies (WFNS) scale is widely accepted for predicting outcomes for subarachnoid hemorrhage (SAH) patients. However, it is difficult to definitely predict outcomes for the most poor grade, WFNS grade 5. The present study aimed to investigate the prognostic ability of a novel classification using computed tomography perfusion (CTP) findings, called the cortical blood flow insufficiency (CBFI) scores. METHODS: CTP was performed on admission for aneurysmal SAH followed by radical treatments within 72 hours of onset. Twenty-four cerebral cortex regions of interest (ROIs) were defined. CBFI was defined as Tmax > 4 s in each ROI, and CBFI scores were calculated based on the total number of ROIs with CBFI. Using the optimal cutoff value based on receiver operating characteristics (ROC) analysis to predict patient functional outcomes, CBFI scores were divided into "high" or "low" CBFI scores. Patient functional outcomes at 90 days were categorized based on modified Rankin Scale scores (0-3, favorable group; 4-6 unfavorable group) (0-4, non-catastrophic group; 5-6, catastrophic group). RESULTS: Fifty-seven patients were included in this study, of whom 21 (36.8%) and 13 (22.8%) were in the unfavorable and the catastrophic groups, respectively. A factor predicting unfavorable and catastrophic outcomes was CBFI score cutoff value of 7 points (area under the curve, 0.73 and 0.81, respectively). In multivariable logistic regression analysis for unfavorable outcome, high CBFI scores (odds ratio (OR), 8.6; 95% confidence interval (CI), 1.1-65.4; P = 0.04) and WFNS grade 5 (OR, 30.0; 95% CI, 4.5-201.0; P < 0.001) remained as independent predictors, while for catastrophic outcome, high CBFI scores (OR, 25.3; 95% CI, 3.3-194.0; P = 0.002) and age (OR, 1.1; 95% CI, 1.0-1.2; P = 0.02) remained as independent predictors. Conversely, WFNS grade 5 was not an independent predictor of catastrophic outcomes (OR, 3.8; 95% CI, 0.6-24.0; P = 0.15). In high CBFI scores, the OR of the delayed cerebral ischemia (DCI) occurrence was 9.6 (95% CI, 1.5-61.4; P = 0.02) after adjusting for age. CONCLUSION: High CBFI scores could predict unfavorable and catastrophic outcomes for aneurysmal SAH patients and DCI occurrence.

Comparison of Landiolol and Digoxin as an Intravenous Drug for Controlling the Heart Rate in Patients with Atrial Fibrillation and Severely Depressed Left Ventricular Function.

Clinical experience with landiolol use in patients with atrial fibrillation (AF) and a severely depressed left ventricular (LV) function is limited. We compared the efficacy and safety of landiolol with that of digoxin as an intravenous drug in controlling the heart rate (HR) during AF associated with a very low LV ejection fraction (LVEF).We retrospectively analyzed 53 patients treated with landiolol (n = 34) or digoxin (n = 19) for AF tachycardias with an LVEF ≤ 25. The landiolol dose was adjusted between 0.5 and 10 µg/kg/minute according to the patient's condition. The response to treatment was defined as a decrease in the HR of ≤ 110/minute, and that decreased by ≥ 20% from baseline.There were no significant differences between the two groups regarding the clinical characteristics. The responder rate to landiolol at 24 hours was significantly higher than that to digoxin (71.0% versus 41.2%; odds ratio: 4.65, 95% confidence interval: 1.47-31.0, P = 0.048). The percent decrease in the HR from baseline at 1, 2, 12, and 24 hours was greater in the landiolol group than in the digoxin group (P < 0.01, P = 0.071, P = 0.036, and P = 0.016, respectively). The systolic blood pressure (SBP) from baseline within 24 hours after administering landiolol was significantly reduced, whereas digoxin did not decrease the SBP over time. Hypotension (< 80 mmHg) occurred in two patients in the landiolol group and 0 in the digoxin group (P = 0.53).Landiolol could be more effective in controlling the AF HR than digoxin even in patients with severely depressed LV function. However, careful hemodynamic monitoring is necessary when administering landiolol.

Comparison of the Transdermal Bisoprolol Patch with Oral Bisoprolol Fumarate Administration as a Therapeutic Agent for Idiopathic Frequent Premature Ventricular Contractions.

The transdermal bisoprolol patch (TB) was designed to maintain a sustained concentration of bisoprolol in plasma by a higher trough concentration than oral bisoporolol (OB). We compared the efficacy between TB and OB in patients with idiopathic premature ventricular contractions (PVCs) while considering their duration of action.A total of 78 patients with a PVC count of ≥ 3,000 beats/24 hours were divided into groups treated with TB 4 mg (n = 43) or OB 2.5 mg (n = 35). PVCs were divided into positive heart rate (HR) -dependent PVCs (P-PVCs) and non-positive HR-dependent PVCs (NP-PVCs) based on the relationship between the hourly PVC density and hourly mean HR. Twenty-four-hour Holter electrocardiograms were performed before and 1 to 3 months after the initiation of therapy.There were no significant between-group differences in the baseline characteristics. Both the TB (from 14.6 [9.9-19.2] to 7.6 [1.7-15.8]%, P < 0.001) and OB (from 13.2 [7.6-21.9] to 4.6 [0.5-17.0]%, P = 0.0041) significantly decreased the PVC density, and there was no significant difference between the two groups (P = 0.73). Compared to OB, the TB had similar effects in reducing the PVC density for P-PVCs (P = 0.96), and NP-PVCs (P = 0.71). The TB significantly decreased the P-PVC density from baseline not only during day-time (P < 0.001) but also night-time (P = 0.0017), while the OB did not significantly decrease the P-PVC density from baseline during night-time (P = 0.17).Compared to OB, the TB could be used with the same efficacy of reducing idiopathic PVCs. The TB may be a more useful therapeutic agent than OB for P-PVCs during a 24-hour period.

Experimental Analysis of Intra-luminal Pressure by Contrast Injection during Mechanical Thrombectomy: Simulation of Rupture Risk of Hidden Cerebral Aneurysm in Tandem Occlusion with Blind Alley.

Mechanical thrombectomy using a retrograde approach is performed for tandem occlusion of the internal carotid artery (ICA). In our patient, a guiding catheter was easily passed by the stenosed lesion despite severe stenosis at the ICA origin. Therefore, we aimed to recanalize the occlusion of the terminal ICA without angioplasty for the stenosed lesion. When contrast was injected, a massive extravasation of contrast from the C2 portion of the ICA was observed. It was speculated that the bleeding was caused by rupture of an aneurysm at that site due to increased intra-arterial pressure caused by the contrast injection to a blind alley, which was created by a wedged guiding catheter at severe stenosis at the ICA origin and the occlusion of the terminal ICA. Our simulation experiment using a silicon vascular model in this situation demonstrated that the elevation of intra-arterial pressure in such blind alley reached over 50, 100, and 200 mmHg by injection of contrast from a microcatheter, a 4-Fr inner catheter, and a 9-Fr balloon-guiding catheter, respectively. When a retrograde approach is planned for tandem occlusion of the ICA, even when the proximal lesion is easily passed, prior angioplasty for the proximal lesion should be considered to avoid wedging by catheter.

Clinical Factors Associated with a Successful Catheter Ablation Outcome in Elderly Patients with Atrial Fibrillation.

Catheter ablation is currently an established treatment for symptomatic paroxysmal atrial fibrillation (AF). We focused on elderly patients with a high prevalence of AF and attempted to identify the clinical factors associated with unsuccessful ablation outcomes.Among 735 consecutive patients who underwent AF ablation procedures, 108 (14.7%, 66 men) aged ≥ 75 years were included. Of them, 80 had paroxysmal AF, and the remaining 28 non-paroxysmal AF. All patients underwent pulmonary vein (PV) isolation and occasionally additional ablation. When AF recurred, redo ablation procedures were performed if the patient so desired.The mean number of ablation procedures was 1.1 ± 0.4 times per patient. During a mean follow-up of 38.7 ± 21.7 months, sinus rhythm was maintained in 100 patients (92.6%) without any antiarrhythmic drugs, but not in the remaining 8 (7.4%). Left atrial diameter (LAD, P < 0.001), left ventricular (LV) systolic diameter (P < 0.001), LV diastolic diameter (P = 0.001), non-PV AF foci (P = 0.036), and diabetes (P = 0.045) were associated with unsuccessful ablation procedures. Multivariate logistic regression analysis revealed a large LAD and non-PV AF foci were significant independent predictors of AF recurrences, with odds ratios of 0.76 (P = 0.019) and 0.04 (P = 0.023), respectively. In a total of 124 procedures, one major (0.8%) and 11 minor (8.9%) complications occurred.In elderly AF patients, catheter ablation of AF is effective and safe. Non-PV AF foci and a large LAD were independent clinical predictors of unsuccessful AF ablation outcomes.

The Difference in the Changes of Indoxyl Sulfate after Catheter Ablation among Atrial Fibrillation Patients with and without Kidney Dysfunction.

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces chronic kidney disease (CKD) and atrial fibrillation (AF). Catheter ablation (CA) of AF improves the renal function. However, the transition of uremic toxins is unclear. This study aimed to investigate the transition of the serum IS level in AF patients with and without CKD after CA. A total of 138 consecutive AF patients who underwent CA and maintained sinus rhythm were prospectively enrolled (paroxysmal AF 67.4%). The patients were divided into 4 groups (non-CKD/low-IS:68, non-CKD/high-IS:28, CKD/low-IS:13, and CKD/high-IS:29). The plasma IS levels and estimated glomerular filtration rate (eGFR) were determined before and 1-year after CA. CKD was defined as CKD stage III and a high-IS according to the mean IS (IS ≥ 1.1 µg/ml). CA significantly improved the eGFR in CKD patients (p < 0.001). The serum IS level in the non-CKD/high-IS group was significantly decreased (from 1.7 ± 0.7 to 1.1 ± 0.6 µg/ml, p < 0.001). However, the serum IS level in the CKD/high-IS group did not improve (from 1.9 ± 0.9 to 1.7 ± 0.7 µg/ml, p = 0.22). The change in the IS in the CKD patients significantly differed from that in those without CKD. In the CKD patients, CA did not significantly decrease the IS, a risk factor of CKD, regardless of an improved eGFR.

Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty.

BACKGROUND: The safety and efficacy of an oral anticoagulant (OAC) treatment and the difference between direct OACs (DOACs) and warfarin in nonsevere frail elderly patients with AF are unclear. METHODS: This was a retrospective and observational study of 354 patients over 80 years of age with nonsevere frailty who were diagnosed with AF and treated with OACs. Nonsevere frailty was defined as a clinical frailty scale score of <7. Bleeding and thromboembolic events during the OAC treatment were followed up. RESULTS: Of 354 patients enrolled, 273 (77.1%) received DOACs and 81 (22.9%) received warfarin. Of 273 patients receiving DOACs, there were 210 (76.9%) prescribed with appropriate doses of DOACs. Of 81 warfarin-treated patients, 53 (65.4%) were prescribed an appropriate dose of warfarin. During a follow-up of 33.1 (14.0-51.0) months, 15 patients (1.5/100 person-years) had bleeding events and 10 (1.0/100 person-years) had thromboembolic events while on an OAC treatment. The incidence ratio of bleeding events in patients receiving DOACs was lower than that in those receiving warfarin (1.0/100 person-years vs 2.9/100 person-years, hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.07-0.91, P = .036). There was no significant difference in the incidence of thromboembolic events between the DOAC and warfarin treatment groups (0.88/100 person-years vs 1.4/100 person-years, HR: 0.63, 95% CI: 0.16-2.57, P = .52). CONCLUSIONS: OACs are substantially safe and effective for preventing thromboembolic events in nonsevere frail patients over 80 years of age. Particularly, DOACs can be used more safely than warfarin.

Prosthesis Used in Microvascular Decompressions: A Multicenter Survey in Japan Focusing on Adverse Events.

OBJECTIVE: To investigate the characteristics of materials used as prostheses for microvascular decompression surgery (MVDs) in Japan and their possible adverse events (AEs) to determine preferable materials for MVDs. METHODS: A questionnaire was sent to all members of the Japanese Society for MVDs, and answers were obtained from 59 institutions. RESULTS: Among a total of 2789 MVDs, 1088 operations for trigeminal neuralgia, 1670 for hemifacial spasm, and 31 others, including 117 reoperations, were performed between April 2011 and March 2014. Nonabsorbable material was used in 96.5% of MVDs, including polytetrafluoroethylene (PTFE) (80.5%), polyurethane (11.9%), expanded PTFE (2.1%), and silk thread (1.47%). The use of absorbable materials, including fibrin glue (87.5%), cellulose (13.5%), gelatin (4,77%), and collagen (1.76%), was reported. The major combinations were PTFE with fibrin glue (58.7%) followed by PTFE alone (7.60%). Eighty-eight AEs in 85 (3.2%) cases were reported among 2672 first operations. AEs included 51 central nervous system dysfunctions, 15 wound infections/dehiscence, and 10 others, which were presumed to be related to the intraoperative procedure. Among relatively high-, moderate-, and low-volume centers, there were no significant differences in the frequency of AEs (P = 0.077). Tissue-prosthesis adhesion and/or granuloma formation were reported in 13 cases of 117 reoperations. The incidence of adhesion-related recurrence was 11.1% of all reoperations. CONCLUSIONS: The number of AEs was quite low in this survey, and intradural use of any prosthesis reported in this paper might be justified; however, further development of easily handled and less-adhesive prosthesis materials is awaited.

Assessment of the bleeding risk of anticoagulant treatment in non-severe frail octogenarians with atrial fibrillation.

BACKGROUND: Physicians estimate the frailty in elderly patients with atrial fibrillation (AF) to aid in the decision making with respect to oral anticoagulant (OAC) therapy. There are limited data on the safety of OAC therapy in non-severe frail elderly patients. We evaluated the risk factors of bleeding among non-severe frail octogenarians with AF taking OACs. METHODS: Among 430 consecutive AF patients aged 80 years and over with non-severe frailty, we enrolled 346 patients [167 men, 83.7 (81.0-85.0) years] who were newly initiated on OACs: dabigatran, rivaroxaban, apixaban, edoxaban, or warfarin. To measure the frailty, the clinical frailty scale (CFS) was used. Non-severe frailty was defined as a CFS score of <7. The clinical factors were compared between the patients with and without bleeding during the OAC therapy. RESULTS: Out of the 346 patients enrolled, 266 (76.9%) received direct OACs (DOACs) and 80 (23.1%) warfarin. Of the 266 patients receiving DOACs, there were 204 (76.7%) prescribed appropriately adjusted-dose DOACs based on the approved Japanese recommendations. Of the 80 warfarin-treated patients, 52 (65.0%) were prescribed appropriately adjusted-dose warfarin. During a follow-up of 32.7 (14.0-51.0) months, bleeding events were detected in 59 patients (17.1%). Among the clinical factors, a multivariate analysis found that having a low body mass index (BMI) (<18.5kg/m2) was associated with the development of bleeding [hazard ratio (HR): 3.26, 95% confidence interval (CI): 1.65-6.50, p<0.01)]. Moreover, having a low BMI remained an independent risk factor for bleeding in the patients treated with appropriately adjusted-dose OACs (HR: 2.17, 95% CI: 1.01-4.70, p=0.048). CONCLUSIONS: In non-severe frail octogenarians with AF taking OACs, having a low BMI was the most significant factor associated with the development of bleeding.

The relationship between serum indoxyl sulfate and the renal function after catheter ablation of atrial fibrillation in patients with mild renal dysfunction.

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces renal disorders and atrial fibrillation (AF). It is well known that renal dysfunction is a risk factor for AF and radiofrequency catheter ablation (RFCA) improves the renal function. However, the improvement in the renal function after RFCA in patients with early stage chronic kidney disease (CKD) and the serial changes in the IS level have not been fully elucidated. This study aimed to investigate whether IS affects the improvement in the renal function. A total of 91 consecutive patients with mild kidney dysfunction (CKD stage I-II) who underwent RFCA and maintained sinus rhythm were prospectively enrolled. The plasma IS level and estimated glomerular filtration rate (eGFR) were determined before, 3 months, and 1 year after RFCA. The patients were divided according to the IS quartiles (Q1-4; < 0.4, 0.4-0.7, 0.7-1.2, and > 1.2 µg/ml). There was no significant difference in the eGFR among the IS quartiles. A significantly higher eGFR improvement rate was obtained for IS-Q4 than the other quartiles (p = 0.039). The IS-Q4 IS level significantly decreased at 1 year after RFCA (1.8 ± 0.8 to 1.2 ± 0.7 µg/ml, p < 0.01). The multivariable logistic model revealed that a high-IS level (IS-Q4) was an independent predictor of an eGFR improvement (OR 3.33; 95% CI 1.16-9.59; p = 0.026). A high-IS level reduction after RFCA improved the renal function in AF patients with mild kidney dysfunction.

Right Ventricular Septal Pacing Using a Thin Lumenless Pacing Lead and Delivery System with a Deflectable Catheter.

The SelectSecure™ lead system (SSLS), which is composed of a thin lumenless, active-fixation lead and a deflectable catheter, is approved for use in Japan. This study aimed to evaluate the long-term clinical outcomes of right ventricular (RV) septal pacing with the SSLS along with the system's safety and electrical performance. A total of 129 patients were divided into the following 3 groups: the RV septal pacing with the SSLS group (SSP, n = 21); the RV septal pacing with the conventional lead group (Septal, n = 77); and the RV apical pacing with the conventional lead group (Apical, n = 31). All lead-related complications and pacing parameters during follow-up were compared among the groups. The clinical outcome was heart failure-associated hospitalization. The SSP and Septal groups showed significantly shorter paced QRS duration than the Apical group. During the follow-up for a mean of 49.5 ± 13.1 months, no lead-related complications occurred in any of the groups. A case of pericardial effusion occurred in the SSP group, but cardiac tamponade did not occur, and it spontaneously resolved. The ventricular pacing threshold after the follow-up period was higher in the SSP group than in the other 2 groups. There was no difference in the primary heart failure hospitalization among the 3 groups. The SSLS could be effective in producing a narrow QRS width with RV septal pacing, but its pacing threshold was higher than conventional leads in the chronic phase.

Bleeding with oral anticoagulant dabigatran is highly associated with occult cancers in atrial fibrillation patients.

AIM: The aim of this study was to examine cancer and bleeding in atrial fibrillation patients administered with dabigatran. MATERIALS & METHODS: This study enrolled 509 consecutive nonvalvular atrial fibrillation patients who received dabigatran. The mean administration period was 14.8 ± 15.7 months. We investigated the prevalence and new development of cancers. Further, the relation between cancer and adverse events was evaluated. RESULTS: In the 509 patients, major bleeding occurred in 2.6% and dyspepsia in 8.4%. Further, 16.9% patients had a history of cancer and 3.9% developed new cancers. These adverse events developed in 45% patients who developed new cancers. The cancer (hazard ratio: 6.30; p = 0.003) was a significant predictor of major bleeding. CONCLUSION: Bleeding was associated with the presence of cancer.

Assessment of a novel transdermal selective ß1-blocker, the bisoprolol patch, for treating frequent premature ventricular contractions in patients without structural heart disease.

BACKGROUND: The autonomic nervous system involves the genesis of premature ventricular contractions (PVCs). Previous studies demonstrated that heart rate (HR) dependency of idiopathic PVCs has different autonomic mechanisms. Recently, the bisoprolol patch, a novel transdermal ß1-blocker formulation containing bisoprolol, became clinically available. We examined the efficacy of the bisoprolol patch for treating frequent PVCs in patients without structural heart disease (SHD) regarding the HR dependency of PVCs. METHODS: This prospective study included 44 consecutive patients without SHD (25 men, mean age, 63.6±12.3 years) with PVC counts≥3000 beats as measured by 24-hour Holter electrocardiograms (ECGs). PVCs were divided into positive HR-dependent PVCs (P-PVCs) and non-positive HR-dependent PVCs (NP-PVCs) based on the relationship between the hourly PVC density and hourly mean HR. A bisoprolol patch was administered once daily at a dose of 4mg. The 24-hour Holter ECGs were performed before and 1 month after the initiation of the therapy. RESULTS: In 44 patients, there were 24 P-PVCs and 20 NP-PVCs. The bisoprolol patch reduced the PVC count significantly (from 16,563±10,056 to 7892±8817 beats/24hours, p<0.001) in the P-PVC group, while the PVC count did not change significantly (from 16,409±9571 to 13,476±12,191beats/24hours, p=0.34) in the NP-PVC group. Moreover, in the P-PVC group, the patients with mean HRs ≥80 beats/minute had a significantly higher percent improvement in the PVC count than those with mean HRs <80 beats/minute (p=0.0080). The bisoprolol patch resulted in a significant reduction in the PVC count from baseline during each time period for the changes within a 24-hour period in the P-PVC group. CONCLUSIONS: The transdermal bisoprolol patch was effective for a PVC reduction in patients with P-PVCs, particularly in those with faster mean HRs. Furthermore, it demonstrated a stable PVC-reducing effect during the 24-hour period in the P-PVC group.