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.

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

BACKGROUND: 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. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters. RESULTS: Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments. CONCLUSIONS: DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.

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.

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.

Evaluation of sympathetic activity by 123I-metaiodobenzylguanidine myocardial scintigraphy in dilated cardiomyopathy patients with sleep breathing disorder.

BACKGROUND: Because increased sympathetic nervous activity (SNA) in patients with dilated cardiomyopathy (DCM) associated with sleep breathing disorder (SBD) is known to deteriorate the prognosis of cardiac failure, (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was used as the investigative tool in the present study. METHODS AND RESULTS: The study group comprised 53 patients (47 men, 6 women; mean age 56+/-3 years) with chronic stable DCM. Patients were divided into SBD(+) or SBD(-) group according to 24-h pulse oximetry results. SBD(+) was defined when the 3% oxygen desaturation index was more than 15/h during sleep. In total, 32 patients were SBD(-) and 21 were SBD(+). In both groups, pulse oximetry were performed during sleep and awakening pulse rate, and measurement of the blood levels of catecholamines and B-type natriuretic peptide was performed. MIBG myocardial scintigraphy and echocardiography were performed at the same time. No significant difference was found between the 2 groups in catecholamine levels or left ventricular ejection fraction. However, MIBG had a significantly increased washout rate and a significantly decreased delayed heart to mediastinum ratio in the SBD(+) group compared with the SBD(-) group. CONCLUSIONS: SNA is increased in DCM patients when associated with SBD. MIBG myocardial scintigraphy may be a sensitive method of detecting increased SNA.