Effectiveness of suvorexant versus benzodiazepine receptor agonist sleep drugs in reducing the risk of hip fracture: Findings from a regional population-based cohort study.

Sleep drugs are often necessary to treat insomnia in older patients. Benzodiazepine receptor agonists (BZRAs) are primarily used for insomnia in these patients, but there are concerns regarding their association with delirium and bone fractures. Among sleep drugs, orexin receptor antagonists such as suvorexant have a lower risk of delirium than BZRAs, but their effectiveness in preventing hip fractures is unknown. Hip fracture is a life-threatening trauma in advanced-age patients and a social problem. Therefore, we investigated the relationship between suvorexant and hip fracture. The Shizuoka Kokuho Database was used to compare the time to hip fracture in patients who had been newly taking suvorexant and other sleep drugs such as benzodiazepines since November 2014. A proportional hazards model for hip fracture as an outcome was used to estimate the hazard ratio. Propensity scores were estimated using a logistic regression model, and the confounding factors were age, sex, several comorbidities, and each oral medication. The suvorexant group comprised 6860 patients (110 with hip fracture), and the BZRA group (benzodiazepines and Z-drugs) comprised 50,203 patients (1487 with hip fracture). In the matched cohort (6855:6855 patients), 259 and 249 patients in the suvorexant and BZRA group developed hip fractures during the observational period, respectively. The hazard ratio of the suvorexant group compared with the BZRA group was 1.48 (95% confidence interval, 1.20-1.82). In the subgroup analysis, patients in the suvorexant group had a higher risk of hip fracture if they were aged >75 years, had no diabetes, had no neurological disease, had no renal failure, had liver disease, had hypertension, were not taking alpha 1 blockers, and were not taking oral steroids. Among people in the Japanese regional population who use sleep drugs, patients taking suvorexant can be at higher risk of hip fracture than patients taking BZRAs.

Usefulness of entrainment mapping using the activation sequence of the last captured excitation in complex dual-loop atrial tachycardia.

BACKGROUND: Electroanatomical mapping is useful for locating the atrial reentrant circuit, but analysis of the dynamic relation of the reentrant circuit is sometimes difficult. This article describes three cases of complex dual-loop reentrant atrial tachycardia analyzed by entrainment mapping using not only the postpacing interval (PPI) but also the activation sequence of the last captured beats. METHODS: Case 1 was dual-loop reentry consisting of the tricuspid annulus (TA) and a localized atrial reentry at the coronary sinus (CS) ostium with different exit sites to the right and the left atrium that was cured by catheter ablation at the CS ostium showing fractionated potential. Case 2 was dual-loop reentry around the TA and the superior trans-septal incision line. Case 3 was dual-loop reentry around the TA and longitudinal dissociation along the cavo-tricuspid isthmus. RESULTS: In Cases 1 and 2, entrainment with a shorter pacing cycle length demonstrated antidromic penetration to the circuit and changed the activation sequence of the last captured beat depending on the anatomical relation of the reentrant circuit. In Cases 1-3 with dual-loop reentry, the excitation wavefront induced by stimulation entered one circuit after going around the other; thus, the penetration to the other reentry circuit became the second beat after the stimulus (one lap behind). CONCLUSIONS: The PPI is obtained from the pacing site only, but the last captured beat could be obtained from all electrodes. It is advantageous to use the information from all available electrode recordings to determine the dynamic relation between complex dual-loop reentrant circuits.

Evaluation of repolarization dynamics using the QT-RR regression line slope and intercept relationship during 24-h Holter ECG.

QT-RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT-RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT-RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p < 0.001) and the intercept was significantly smaller in women than in men (0.229 ± 0.028 vs. 0.240 ± 0.027, p < 0.001). A scatter diagram of the QT-RR regression line slope and intercept among healthy subjects demonstrated a statistically significant negative correlation (B = -0.62A + 0.34, r = -0.79). Distribution of both scatter diagrams of the slope and the intercept of the QT-RR regression line in patients with IVF and TDP was different from healthy subjects (left corner for IVF and upward shift for TDP). The slope and intercept relationship of the QT-RR linear regression line based on 24-h Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.

High prevalence of cyclical variation in heart rate before nocturnal episodes of paroxysmal atrial fibrillation.

OBJECTIVE: Nighttime onset of atrial fibrillation (AF) is sometimes associated with obstructive sleep apnea accompanied by a characteristic heart rate (HR) pattern known as cyclical variation of HR. The aim of this study was to evaluate whether cyclical variation of HR is prevalent in patients with nocturnal AF. METHODS: The subjects consisted of 34 patients (68±12 years) with paroxysmal AF, including 14 patients with daytime AF and 20 patients with nighttime AF. Holter electrocardiogram (ECGs) were examined for the presence of cyclical variation in HR and to quantify the HR variability within the 40-minute period preceding each AF episode using a fast Fourier transform (FFT) methods. RESULTS: Cyclical variation in HR was observed in 12 of 20 (60%) nighttime episodes and in only two of 14 (14%) daytime episodes. The prevalence of cyclical variation in HR was significantly greater in the nighttime AF episodes than in the daytime AF episodes (Chi=5.34, p<0.05). The mean frequency of cyclical variation in HR was 0.015±0.003 Hz. The mean power of the VLF (very low frequency) component (0.008-0.04 Hz) before the onset of AF was significantly greater in the nighttime AF episodes than in the daytime AF episodes. Among the nighttime AF episodes, the power of the HF (high frequency), LF (low frequency) and very low frequency (VLF) components increased significantly just before the onset of AF compared with that observed 40 minutes before onset. CONCLUSION: The high prevalence of cyclical variation in HR observed before nocturnal AF episodes suggests that sleep apnea may play a role in the onset of nighttime AF.

Sick sinus syndrome induced by interferon and ribavirin therapy in a patient with chronic hepatitis C.

The therapeutic effect of interferon (IFN) on chronic hepatitis C and its adverse effects have been well documented. Although the incidence of IFN-related cardiotoxicity is low, careful observation is necessary because of its possible fatal outcome. We describe a 45-year-old woman who suffered from sinus node dysfunction after the combination therapy of pegylated IFN-alpha and ribavirin for chronic hepatitis C. Despite the cessation of IFN therapy, sinus node dysfunction was not reversible, and led her to the implantation of permanent pacemaker. Physicians should therefore be aware of the possibility of sinus node dysfunction in patients receiving IFN therapy. .

QT/RR relation during atrial fibrillation based on a single beat analysis in 24-h Holter ECG: the role of the second and further preceding RR intervals in QT modification.

BACKGROUND: During atrial fibrillation (AF) irregularity of RR intervals may modify QT/RR relation differently from sinus rhythm. The purpose of this study was to compare QT/RR relation based on a single-beat analysis using the first preceding RR interval with the modified RR interval reflecting not only the first preceding but also the second and further preceding RR intervals during AF. METHODS: QT and RR intervals were measured using an automatic QT analyzing system in 32 patients who had both AF and sinus rhythm on the same 24-h Holter ECG recording. In 12 patients antiarrhythmic drugs (AADs) were administered. To reflect irregularity of the preceding RR intervals during AF, a modified RR (mRR) using a weighted average of five successive RR intervals: (5RR(1)+2RR(2)+RR(3)+RR(4)+RR(5))/10 was adopted. Linear regression analyses between QT and RR intervals were performed using the preceding RR(1) (QT/RR) and the modified RR (QT/mRR) during AF. RESULTS: During AF the slope of QT/RR was lower than that of QT/mRR and was also lower than that of QT/RR during sinus rhythm in patients with and without AAD. Slopes of regression line in QT/RR during sinus rhythm, QT/RR and QT/mRR during AF were steeper in patients with AAD than those in patients without. Slopes of QT/RR during sinus rhythm correlated with those of QT/mRR (r=0.79, p<0.01) better than those of QT/RR (r=0.64, p<0.05) during AF. QT interval at an RR interval of 1.20s or 1.00 s obtained from QT/RR during AF was significantly smaller than that during sinus rhythm in patients with and without AAD. CONCLUSIONS: The slope of QT/mRR during AF became closer to that of QT/RR during sinus rhythm compared with that of QT/RR during AF. QT interval during sinus rhythm could be estimated better using QT/mRR than using QT/RR during AF.

Torsades de pointes induced by garenoxacin in association with pacing failure in an elderly woman with VDD pacemaker.

An 86-year-old woman was admitted to the hospital for syncope and convulsion 4 days after starting antibiotic therapy for pneumonia with oral garenoxacin 400 mg/day. She had a VDD pacemaker for complete atrioventricular (AV) block. Her electrocardiogram showed marked QT prolongation and during pacemaker interrogation pacing failure probably due to battery depletion induced torsades de pointes. After cessation of garenoxacin, QTc returned to normal range subsequently and a new pacemaker was implanted. In patients with risks of QT prolongation, garenoxacin should be used cautiously with QT interval monitoring.