Kenzaburo Kobayashi

Comparison of late potentials for 24 hours between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy using a novel signal-averaging system based on Holter ECG.

Background— Late potentials (LP) detected with signal-averaged ECGs are known to be useful in identifying patients at risk of Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the pathophysiology is clearly different between these disorders, we clarified the LP characteristics of these disorders. Methods and Results— This study included 15 BS and 12 ARVC patients and 20 healthy controls. All BS patients had characteristic ECG changes and symptomatic episodes. All ARVC patients had findings that were consistent with recent criteria. Three LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 µV] in the terminal, filtered QRS complex) were continuously measured for 24 hours using a novel Holter-based signal-averaged ECG system. The incidences of LP determination in BS (80%) and ARVC (91%) patients were higher than in healthy controls (5%; P<0.0001 in both) but did not differ between BS and ARVC patients. In BS patients, the dynamic changes of all LP parameters were observed, and they were pronounced at nighttime. On the contrary, these findings were not observed in ARVC patients. When the SD values of the 3 LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 µV] in the terminal, filtered QRS complex) over 24 hours were compared for the 2 patient groups, those values in BS patients were significantly greater than those in ARVC patients (P<0.0001 in all). Conclusions— LP characteristics detected by the Holter-based signal-averaged ECG system over 24 hours differ between BS and ARVC patients. Dynamic daily variations of LPs were seen only in BS patients. This may imply that mechanisms of lethal ventricular arrhythmia in BS may be more correlated with autonomic abnormality than that of ARVC.

Defibrillation Effects of Intravenous Nifekalant in Patients with Out‐of‐Hospital Ventricular Fibrillation

Nifekalant (NF), a pure K+ channel blocker developed in Japan, has been reported to be effective in the treatment of life‐threatening ventricular arrhythmias. We studied its efficacy in 18 men and 4 women with out‐of‐hospital ventricular fibrillation (VF) admitted to our emergency department between August 2001 and March 2004. The number of DC shocks delivered for out‐of‐hospital VF, serum Na+ and K+, arterial blood pH, and base excess were compared in 8 patients treated with NF, 0.3 mg/kg i.v. followed by a continuous intravenous (group N) versus 14 patients treated with lidocaine, 2 mg/kg, i.v. (group C). The two groups were similar with respect to their baseline characteristics. Sinus rhythm returned in 5 of 8 patients in group N versus 2 of 14 patients in group C (P < 0.05). These seven patients were admitted to the intensive care unit, though all died within 1 month. The results of this study suggest that NF may be effective in defibrillation of out‐of‐hospital VF, though controlled studies are needed to confirm our observations.

Efficacy of Dabigatran for Dissolving Deep Vein Thromboses in Outpatients With a Deteriorated General Condition:A Single Center Experience

Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for the prevention of ischemic strokes in patients with nonvalvular atrial fibrillation (AF). At present, NOACs have been evaluated for the treatment of deep vein thrombosis (DVT). We examined the efficacy of dabigatran, the first NOAC for anticoagulation of AF in Japan, in outpatients who suffered from DVTs under a deteriorated general condition.Thirty-six consecutive outpatients diagnosed with DVT at our institute were enrolled. Not all patients could be hospitalized due to other clinical problems; 15 (42%) had malignant tumors, 9 (25%) psychological disorders, and 6 (17%) postoperative orthopedic disease. Dabigatran was administered at a dose of 110-150 mg once or twice daily, depending on the renal function and age. The mean dosage of dabigatran was 211.7 ± 36.6 mg per day. In 18 (50%) patients, the DVTs were completely dissolved and disappeared over a treatment term of 4.3 ± 4.3 months. In 9 patients (25%), the DVTs partly dissolved, but in the remaining 9 (25%) patients, dabigatran was totally ineffective. During a follow-up of 30.5 ± 5.3 months, DVTs did not recur with dabigatran in 18 patients with an effective efficacy. In a multivariate analysis, patients with small sized thromboses and those without malignant tumors were significantly associated with the DVTs dissolving (P = 0.003 and P = 0.006, respectively).Dabigatran was effective for dissolving DVTs in outpatients with a poor condition, particularly when the size of the DVT was small and malignant tumors were absent.

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

BACKGROUNDnPhysicians 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.nnnMETHODSnAmong 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.nnnRESULTSnOut 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).nnnCONCLUSIONSnIn non-severe frail octogenarians with AF taking OACs, having a low BMI was the most significant factor associated with the development of bleeding.

Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias

Pilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug‐induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide.

Assessment of a novel transdermal selective β1-blocker, the bisoprolol patch, for treating frequent premature ventricular contractions in patients without structural heart disease

BACKGROUNDnThe 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 β1-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.nnnMETHODSnThis 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnThe 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.

Obesity Is Associated With the Development of Interstitial Pneumonia Under Long-Term Administration of Amiodarone in Refractory Atrial Fibrillation Patients.

Although oral amiodarone (AMD) has been used for the management of atrial fibrillation (AF), serious complications such as interstitial pneumonia (IP) occur very occasionally. We evaluated which factors were associated with the development of IP under the long-term administration of AMD in patients with refractory AF.This study included 122 consecutive patients (65.8 ± 11.4 years, mean body mass index [BMI] of 23.2 ± 4.3 kg/m(2)) who orally received AMD to inhibit AF between January 2004 and December 2013. Administration of AMD was begun at 400 mg daily as a loading dose, and was continued at a dosage of 50-400 mg daily after the initial loading phase, determined by the control of the arrhythmias and occurrence of side-effects. The clinical factors were compared between the patients with and without adverse effects, especially IP.During an average follow-up period of 49.2 ± 28.2 months, 53 patients (43.4%) were determined to have converted and maintained sinus rhythm. In contrast, adverse effects were detected in 46 patients (37.7%) with AMD. IP occurred in 8 patients (6.6%), thyrotoxicosis in 35 (28.7%), and others in 5 (4.1%). Four (50.0%) out of 8 patients complicated with IP had obesity (BMI > 27 kg/m(2)). Among the clinical factors, only obesity was significantly associated with the development of IP (P = 0.026).In patients with refractory AF, AMD had an antiarrhythmic effect with long-term administration, but greater adverse effects were also observed. Obesity was the most significant factor associated with the development of IP.

Prevalence and prognosis of patients with lone and paroxysmal atrial tachyarrhythmias showing Brugada-type electrocardiograms after class IC antiarrhythmic drug administration but no risk-stratifying factors

Class IC antiarrhythmic drugs, used to prevent paroxysmal atrial tachyarrhythmias (ATs), are well known to effectively unmask the electrocardiogram (ECG) pattern of Brugada syndrome. We used these drugs to investigate the prevalence and prognosis of patients with lone and paroxysmal ATs and Brugada‐type ECGs.