Naruya Ishizue

Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy

PURPOSEnRecent reports have documented the appearance of Brugada-type ST elevation in cases of overdose of antiepileptic drugs (AEDs). However, little is known about changes on electrocardiographs (ECGs) during AED use at therapeutic doses. AEDs may cause Brugada-type ST elevation or J-wave-like intraventricular conduction delays through an ion channel-blocking effect. In the present study, we sought to elucidate ECG abnormalities in patients on AED therapy.nnnMETHODSnThe study population consisted of 120 consecutive patients with epilepsy who continued to take AEDs and had ECGs recorded during these therapies. Their clinical background and ECGs were retrospectively analyzed. Brugada-type ST elevation was classified according to the consensus report on Brugada syndrome. A J-wave-like ECG abnormality was defined as the appearance of notching or slurring of the QRS complex (>0.1mV) in the inferior/lateral leads.nnnRESULTSnOf the 120 patients, 15 (12.5%) exhibited Brugada-type ST elevation and 35 (29.2%) showed a J-wave-like ECG abnormality. Polytherapy with sodium channel-blocking AEDs (e.g., carbamazepine, phenytoin, lamotrigine) was more frequently observed in patients with Brugada-type ST elevation (p=0.048). However, the serum concentrations of these medicines did not differ between patients with and without ECG abnormalities (carbamazepine: 7.9±4.1 vs. 7.2±5.9μg/dL; phenytoin: 12.7±4.1 vs. 15.5±9.5μg/dL, NS).nnnCONCLUSIONnST-T abnormalities were frequently seen in patients using AEDs. The presence of Brugada-type ST elevation was associated with polytherapy with sodium channel-blocking AEDs.

An appropriate shock of the wearable cardioverter-defibrillator in an outpatient setting

The wearable cardioverter‐defibrillator (WCD) represents an alternative clinical approach to prevent sudden cardiac death as a bridge to therapy when making a final decision regarding the need for an implantable cardioverter defibrillator (ICD), especially in patients who are in the so‐called gray zone according to ICD guidelines. Although the WCD system was introduced in Japan in April 2014, data regarding its usage and experience are limited. We report the first case of appropriate shock therapy using the WCD in an outpatient setting in Japan. We describe the case of a 22‐year‐old‐woman who received the first case of successful appropriate WCD shock therapy in an outpatient setting in Japan.

Safety of low-dose dabigatran in patients with atrial fibrillation and mild renal insufficiency

BACKGROUNDnDabigatran etexilate (DE), an effective direct oral anticoagulant for patients with atrial fibrillation (AF), should be carefully used in patients with renal insufficiency. Data on the safety of DE in Japanese real world patients with mildly impaired renal function are limited. We hypothesized that low-dose DE (110mg, twice daily) could be safely used in Japanese AF patients with mildly impaired renal function compared to those with preserved renal function.nnnMETHODS AND RESULTSnOne hundred ninety-six consecutive AF patients taking low-dose DE were retrospectively enrolled in this study, and were divided into two groups: preserved creatinine clearance (CCr ≥50ml/min; n=127) and reduced CCr (30-49ml/min; n=69). Baseline characteristics including CHADS2, CHA2DS2-VASc, and HAS-BLED scores were evaluated. Activated partial thromboplastin time (aPTT) was measured as a surrogate marker of the anticoagulant activity of DE, which was evaluated at 661 time points in total and the data were divided into five time windows after the last DE intake. The incidence of bleeding complications was compared between the two groups of reduced and preserved CCr. Reduced CCr group showed higher age (76.9±6.3 years vs. 67.6±6.7 years), higher CHADS2 (2.6±1.4 vs. 1.8±1.2), higher CHA2DS2-VASc (4.3±1.6 vs. 3.2±1.6), and higher HAS-BLED (2.3±1.0 vs. 2.0±1.0) scores in comparison with preserved CCr group (p<0.01, respectively). There was no difference in aPTT over the entire time windows between the two groups. The incidence of total bleeding events was not significantly different between the two groups (reduced vs. preserved CCr=2/69 vs. 2/127).nnnCONCLUSIONnLow-dose DE was safe in AF patients with mildly reduced CCr.

The J-wave as a Predictor of Life-Threatening Arrhythmia in ICD Patients

The J-wave has been reported to be associated with life-threatening ventricular arrhythmia. However, the clinical implication of the J-wave is still unclear in patients with an implantable cardioverter defibrillator (ICD).The study population consisted of 170 ICD patients (age, 56 ± 16 years, 79.4% male) treated at Kitasato University Hospital between 2003 and 2014. Ventricular fibrillation (VF) and ventricular tachycardia (VT) events were documented via ICD interrogation, and the patients were divided into 3 groups: 1) VF event group, 2) VT event group, and 3) No-event group. To predict VT or VF events, univariate and multivariate analysis of clinical data including ECG findings were performed. A J-wave was defined as the presence of notching or slurring of the QRS complex (≥ 0.1 mV) in inferior/lateral leads. Among the 170 patients examined, 23 experienced VF and 38 experienced VT during 54 ± 39 months follow-up. In the multivariate Cox proportional hazards model, the J-wave was identified as an independent predictor for a VF event (HR: 3.886, 95% CI: 1.313-10.568, P = 0.012). In contrast, BNP (HR: 1.002, 95% CI: 1.000-1.003, P = 0.043) and left ventricular diastolic diameter (HR: 1.039, 95% CI: 1.002-1.081, P = 0.049) were independent predictors for a VT event.The results suggest J-waves in the stable phase in an ECG may be a useful predictor for a VF event in ICD patients.

Efficacy and Limitations of Tachycardia Detection Interval Guided Reprogramming for Reduction of Inappropriate Shock in Implantable Cardioverter-Defibrillator Patients

The avoidance of inappropriate shock therapy is an important clinical issue in implantable cardioverter-defibrillator (ICD) patients. We retrospectively analyzed therapeutic events in ICD patients, and the effect of tachycardia detection interval (TDI) and tachycardia cycle length (TCL) guided reprograming on the reduction of inappropriate ICD therapy. The clinical determinants of after reprogramming were also evaluated.A total of 254 consecutive ICD patients were included in the study, and the incidence of antitachycardia therapy was evaluated during the follow-up period of 27.3 ± 18.7 months. When inappropriate antitachycardia therapy appeared, TDI was reprogrammed not to exceed the detected TCL and the patients continued to be followed-up. Various clinical parameters were compared between patients with and without inappropriate ICD therapy. During the initial follow-up period of 18.6 ± 15.6 months, ICD therapy occurred in 127/254 patients (50%) including inappropriate antitachycardia pacing (ATP) (12.9%) and shock (44.35%). Determinants of initial inappropriate therapy were dilated cardiomyopathy (DCM), history of therapeutic hypothermia, and QRS duration. Of the 61 patients with inappropriate therapy, 24 received TCL guided reprogramming. During the additional observation period of 17.0 ± 16.8 months, inappropriate therapy recurred in 5/24 patients (2 ATP, 3 shocks). The determinant of these inappropriate therapy events after reprogramming was the presence of supraventricular tachycardia.By applying simple TCL and TDI guided reprogramming, inappropriate therapy was reduced by 79%. The determinant of inappropriate therapy after reprogramming was the presence of supraventricular tachycardia.

Discrimination of Paroxysmal and Persistent Atrial Fibrillation in Patients With New-Onset Atrial Fibrillation

Discrimination between paroxysmal and persistent atrial fibrillation (PAF and persistent AF) is important for determining the therapeutic strategy in patients with new-onset AF. We evaluated various clinical factors and P wave morphology to discriminate PAF and persistent AF patients in patients with new-onset AF.The study population consisted of 79 patients with new-onset AF (70.3 ± 10.8 years, female:male 33:46) who were retrospectively selected from 8,632 AF patients in the Kitasato University Hospital ECG storing system. PAF (n = 38) and persistent AF (n = 41) patients were diagnosed by whether the initial PAF episode continued for 1 week. The P wave morphologies were analyzed using the most recent 12 lead-ECG recording of sinus rhythm. P wave dispersion was defined as the difference between the maximum and minimum durations of all leads. Along with these data, various clinical factors were evaluated and compared between PAF and persistent AF patients.Multivariate analysis identified P wave dispersion (56.6 ± 14.8 versus 66.5 ± 12.8 msec, P = 0.002) and left atrial dimension (LAD: 40.2 ± 7.0 versus 47.7 ± 8.2 mm, P < 0.001) as independent factors for discrimination between PAF and persistent AF patients. Combining these two parameters achieved a specificity of 88.9%, a positive predictive value of 81.8%, a sensitivity of 95.3%, and a negative predictive value of 88.9%.In patients with new-onset AF, P wave dispersion and LAD were independent factors for discrimination between PAF and persistent AF.

Linagliptin prevents atrial electrical and structural remodeling in a canine model of atrial fibrillation

Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9xa0mg/kg/day, nu2009=u20098) and pacing control group (nu2009=u20098). Three additional dogs without rapid pacing were assigned into non-pacing group, which was used as sham in this study. In the dogs with rapid pacing, the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated and blood was sampled every week. After the entire protocol, atrial tissue was sampled for histological examinations using HE, Azan, and dihydroethidium (DHE) staining to evaluate any tissue damage or oxidative stress. The pacing control group exhibited a gradual AERP shortening and CV decrease along the time course as previously reported. In the linagliptin group, the AERP shortening was not affected, but the CV decrease was suppressed in comparison to the control group (pu2009<u20090.05). The AF inducibility was increased in the control group and suppressed in the linagliptin group (pu2009<u20090.05). The control group exhibited tissue fibrosis, the degree of which was suppressed in the linagliptin group. DHE staining exhibited suppression of the reactive oxygen species expression in the linagliptin group in comparison to the pacing control group. Linagliptin, a DPP-4-inhibitor, suppressed the AF inducibility, CV decrease, and overexpression of oxidative stress in the canine AF model. Such suppressive effects of linagliptin on AF in the canine model may possibly be related to the anti-oxidative effect.

Pacing failure caused by automatic pacing threshold adjustment system

Ventricular capture management is an automatic pacing threshold adjustment algorithm that automatically measures pacing threshold through detection of the evoked response after a pacing stimulus. Although it is principally designed to save device battery under the maintenance of the patient׳s safety, we experienced a rare case with serious pacing failure due to a weakness of this algorithm. This pacing failure might be explained by a large variation in the ventricular pacing threshold depending on the atrioventricular interval and daily variation of pacing threshold and concomitant steroid use in this patient.

Subacute pneumothorax contralateral to the venous access site associated with atrial lead perforation in a patient who was receiving corticosteroid therapy

Pneumothorax contralateral to the venous access site due to the right atrial lead is an uncommon complication. Concomitant steroid use is known as a risk factor of pacemaker lead perforation. We report a rare case of subacute contralateral pneumothorax due to a screw‐in atrial lead perforation that occurred after dual‐chamber pacemaker implantation in a patient who was receiving steroid therapy. The pneumothorax disappeared, and no recurrence was observed during follow‐up with close observation alone.

Cardiac troponin T as a predictor of cardiac death in patients with left ventricular dysfunction

Cardiac troponin T (cTnT) has been reported to be associated with cardiac mortality.