RR interval variability in the evaluation of ventricular tachycardia and effects of implantable cardioverter defibrillator therapy.

BACKGROUND: An implantable cardioverter defibrillator (ICD) is the most reliable therapeutic device for preventing sudden cardiac death in patients with sustained ventricular tachycardia (VT). Regarding its effectiveness, targeted VT is defined based on the tachyarrhythmia cycle length. However, variations in RR interval variability of VTs may occur. Few studies have reported on VT characteristics and effects of ICD therapy according to the RR interval variability. We aimed to identify the clinical characteristics of VTs and ICD therapy effects according to the RR interval variability. METHODS: We analyzed 821 VT episodes in 69 patients with ICDs or cardiac resynchronization therapy defibrillators. VTs were classified as irregular when the difference between two successive beats was >20 ms in at least one of 10 RR intervals; otherwise, they were classified as regular. We evaluated successful termination using anti-tachycardia pacing (ATP)/shock therapy, spontaneous termination, and acceleration between regular and irregular VTs. The RR interval variability reproducibility rates were evaluated. RESULTS: Regular VT was significantly more successfully terminated than irregular VT by ATP. No significant difference was found in shock therapy or VT acceleration between the regular and irregular VTs. Spontaneous termination occurred significantly more often in irregular than in regular VT cases. The reproducibility rates of RR interval variability in each episode and in all episodes were 89% and 73%, respectively. CONCLUSIONS: ATP therapy showed greater effectiveness for regular than for irregular VT. Spontaneous termination was more common in irregular than in regular VT. RR interval variability of VTs seems to be reproducible.

Inappropriate implantable cardioverter defibrillator shocks-incidence, effect, and implications for driver licensing.

PURPOSE: Patients with implantable cardioverter defibrillators (ICDs) have an ongoing risk of sudden incapacitation that may cause traffic accidents. However, there are limited data on the magnitude of this risk after inappropriate ICD therapies. We studied the rate of syncope associated with inappropriate ICD therapies to provide a scientific basis for formulating driving restrictions. METHODS: Inappropriate ICD therapy event data between 1997 and 2014 from 50 Japanese institutions were analyzed retrospectively. The annual risk of harm (RH) to others posed by a driver with an ICD was calculated for private driving habits. We used a commonly employed annual RH to others of 5 in 100,000 (0.005%) as an acceptable risk threshold. RESULTS: Of the 4089 patients, 772 inappropriate ICD therapies occurred in 417 patients (age 61 ± 15 years, 74% male, and 65% secondary prevention). Patients experiencing inappropriate therapies had a mean number of 1.8 ± 1.5 therapy episodes during a median follow-up period of 3.9 years. No significant differences were found in the age, sex, or number of inappropriate therapies between patients receiving ICDs for primary or secondary prevention. Only three patients (0.7%) experienced syncope associated with inappropriate therapies. The maximum annual RH to others after the first therapy in primary and secondary prevention patients was calculated to be 0.11 in 100,000 and 0.12 in 100,000, respectively. CONCLUSIONS: We found that the annual RH from driving was far below the commonly cited acceptable risk threshold. Our data provide useful information to supplement current recommendations on driving restrictions in ICD patients with private driving habits.

Superior Rhythm Discrimination With the SmartShock Technology Algorithm　- Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial.

BACKGROUND: Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology®(SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). CONCLUSIONS: Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.

Various mechanisms and clinical phenotypes in electrical short circuits of high-voltage devices: report of four cases and review of the literature.

AIMS: An electrical short circuit is a rare complication in a high-voltage implantable cardioverter-defibrillator (ICD). However, the inability of an ICD to deliver appropriate shock therapy can be life-threatening. METHODS AND RESULTS: During the last 2 years, four cases of serious complications related to an electrical short circuit have been reported in Japan. A spark due to an electrical short circuit resulted in the failure of an ICD shock to terminate ventricular tachycardia and total damage to the ICD generator in three of four cases. Two of the four patients died from an electrical short circuit between the right ventricle and superior vena cava (SVC) leads. The others had audible sounds from the ICD generator site and were diagnosed with a lead-to-can abrasion, which was manifested by the arc mark on the surface of the can. CONCLUSION: It is still difficult to predict the occurrence of an electrical short circuit in current ICD systems. To reduce the probability of an electrical short circuit, we suggest the following: (i) avoid lead stress at ICD implantation, (ii) select a single-coil lead instead of a dual-coil lead, or (iii) use a unique algorithm which automatically disconnect can or SVC lead from shock deliver circuit when excessive current was detected.

Feasibility evaluation of a remote monitoring system for implantable cardiac devices in Japan.

The number of implanted cardiac devices has been growing steadily over the last several years. Systems to monitor device data remotely have been introduced with the goal of reducing follow-up burden for both patients and physicians. Since the introduction of telemedicine depends greatly on the situations that are unique to each country, the acceptance of cardiac device remote monitoring in Japan was analyzed.A total of 203 patients who had previously undergone cardiac device implantation were enrolled. The subjects were provided with a CareLink Monitor that performed interrogation and transmission of device data at home, and then the physicians reviewed the data via a website at one and 3 months after baseline visits. A total of 470 transmissions were made. Questionnaires were completed by subjects and physicians to evaluate acceptance, ease of use, and satisfaction with the system. More than 87% of the subjects felt the Monitor was easy to use and nearly all of the physicians were satisfied with the system. A majority of patients felt reassured by having their devices assessed from a remote location and preferred the decreased number of clinic visits that were possible when using the Monitor. The patients spent an average of 168.2 minutes per clinic visit, whereas follow-up time was reduced to 13.0 minutes by remote monitoring. Physician consultation time was reduced by 2.7 minutes.The CareLink Network was well accepted by both the patients and physicians. Underlying issues did emerge, but once they are overcome, the system appears to have great potential to improve the quality of care given by healthcare providers.

Nifekalant versus lidocaine for in-hospital shock-resistant ventricular fibrillation or tachycardia.

OBJECTIVE: To compare the efficacy and safety of nifekalant, a pure class III anti-arrhythmic drug, and lidocaine in patients with shock-resistant in-hospital ventricular fibrillation (VF) or ventricular tachycardia (VT). PATIENTS AND METHODS: Between August 2005 and March 2008, we conducted a prospective, two-arm, cluster observational study, in which participating hospitals were pre-registered either to the nifekalant arm or the lidocaine arm. Patients were enrolled if they had in-hospital VF or VT resistant to at least two defibrillation shocks. Congenital or drug-induced long QT syndrome was excluded. The primary end-point was termination of VF or VT with/without additional shock. The secondary end-points were return of spontaneous circulation (ROSC), 1-month survival and survival to hospital discharge. We also assessed the frequency of adverse events, including asystole, pulseless electrical activity and torsade de pointes. RESULTS: In total, 55 patients were enrolled. After nifekalant, 22 of 27 patients showed termination of VF or VT, as compared with 15 of 28 patients treated with lidocaine with/without additional shock (odds ratio (OR): 3.8; 95% confidence interval (CI): 1.1-13.0; P=0.03). Twenty-three of 27 patients given nifekalant showed ROSC, as compared with 15 of 28 patients given lidocaine (OR: 5.0; 95% CI: 1.4-18.2; P=0.01). There was no difference in 1-month survival or survival to hospital discharge between the nifekalant and lidocaine arms. There was a higher incidence of asystole with lidocaine (7 of 28 patients) than with nifekalant (0 of 27 patients) (P=0.005). Torsade de pointes was not observed. CONCLUSION: Nifekalant was more effective than lidocaine for termination of arrhythmia and for ROSC in patients with shock-resistant in-hospital VF or VT (umin-CTR No. UMIN 000001781).

An autopsy case of the rupture of a giant aneurysm in a saphenous vein graft: 18 years after CABG.

The saphenous vein is a widely used blood vessel for arterial bypass procedures. Failures of saphenous vein aortocoronary bypass grafts are predominantly the result of subsequent vein graft atherosclerotic disease. Rarely saphenous vein grafts undergo aneurysmal degeneration. This report describes a case of a ruptured aneurysm in a saphenous vein graft that occurred in an 82-year-old female who underwent a coronary artery bypass operation 18 years previously. We could not resuscitate her, but describe the autopsy findings in detail.

Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.

Long QT syndrome (LQTS) is an inherited disease involving mutations in the genes encoding a number of cardiac ion channels and a membrane adaptor protein. Among the genes that are responsible for LQTS, KCNE1 and KCNE2 are members of the KCNE family of genes, and function as ancillary subunits of Kv channels. The third KCNE gene, KCNE3, is expressed in cardiac myocytes and interacts with KCNQ1 to change the channel properties. However, KCNE3 has never been linked to LQTS. To investigate the association between KCNE3 and LQTS, we conducted a genetic screening of KCNE3 mutations and single nucleotide polymorphisms (SNPs) in 485 Japanese LQTS probands using DHPLC-WAVE system and direct sequencing. Consequently, we identified two KCNE3 missense mutations, located in the N- and C-terminal domains. The functional effects of these mutations were examined by heterologous expression systems using CHO cells stably expressing KCNQ1. One mutation, p.R99lambdaH was identified in a 76-year-old woman who suffered torsades de pointes (TdP) after administration of disopyramide. Another mutation, p.T4A was identified in a 16-year-old boy and 67-year-old woman. Although the boy carried another KCNH2 mutation, he was asymptomatic. On the other hand, the woman suffered from hypokalemia-induced TdP. In a series of electrophysiological analyses, the KCNQ1(Q1)+KCNE3(E3)-R99lambdaH channel significantly reduced outward current compared to Q1+E3-WT, though the current density of the Q1+E3-T4A channel displayed no statistical significance. This is the first report of KCNE3 mutations associated with LQTS. Screening for variants in the KCNE3 gene is of clinical importance for LQTS patients.

Spatial and topologic distribution of verapamil-sensitive atrial tachycardia originating from the vicinity of the atrioventricular node.

BACKGROUND: Little information exists regarding the precise distribution of verapamil-sensitive atrial tachycardia originating from the vicinity of the atrioventricular node (V-AT). METHODS: In 12 patients with V-AT, we examined the spatial and topologic distribution of tachycardia origin relative to the His bundle (HB) site. The V-AT origin was divided into six areas: anterior (A-HB), posterior (P-HB), superior (S-HB), inferior (I-HB), lateral (L-HB), and septal (SP-HB) portion of HB catheter. Three dimensional distance between the distal pair of the electrodes of HB catheter and that of V-AT origin (DIS) was obtained by calculating the distances on the right and left anterior fluoroscopic images. Topologic distribution was expressed as the interval between the onset of the atrial electrogram of V-AT origin and that of HB catheter (INT). RESULTS: The tachycardia origin was observed at the P-HB in four, S-HB in two, I-HB in two, SP-HB in three, and L-HB in one patient. The tachycardia cycle length, DIS, and INT were 369 +/- 67 ms, 12 +/- 3 mm, and -12 +/- 8 ms, respectively. After successful ablation of initial V-AT (1st V-AT), V-AT with a different origin (2nd V-AT) was induced in five patients. The tachycardia origin, tachycardia cycle length, DIS, and INT of the 2nd V-AT (P-HB in three, S-HB in one, and SP-HB in one patient; 333 +/- 66 ms, 8 +/- 3 mm, and -11 +/- 4 ms, respectively) were not different from those of 1st V-AT. CONCLUSIONS: V-AT often shows a shift in tachycardia origin to another site where the spatial and topologic distributions are similar to those of 1st V-AT.

Impact of right atrial-left ventricular dual-chamber permanent pacing in patients with severely symptomatic hypertrophic obstructive cardiomyopathy.

BACKGROUND: Effective alternatives to surgical myectomy for patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) remain unestablished. Dual-chamber (DDD) pacing was evaluated in these patients using right atrial (RA) and epicardial left ventricular (LV) leads. METHODS AND RESULTS: In 6 patients with HOCM refractory to medical therapy and conventional RA-right ventricular (RV) DDD pacing, we implanted DDD pacemakers using RA and epicardial LV leads. The baseline intraventricular pressure gradient before pacemaker implantation was 103+/-44 mmHg. The pressure gradient decreased significantly to 8+/-16 mmHg by temporary RA-LV DDD pacing (p=0.006), while it decreased only to 68+/-25 mmHg by temporary RA-RV pacing (NS). It was nearly eliminated to 1+/-2 mmHg (p=0.027) 3 months after RA-LV DDD pacemaker implantation. LV end-diastolic pressure, cardiac index and systolic aortic pressure did not change significantly. New York Heart Association class improved in all patients (p=0.023). Brain and atrial natriuretic peptide concentrations, respectively 516+/-286 and 143+/-34 pg/ml at baseline, decreased significantly to 230+/-151 and 93+/-44 pg/ml 3 months after implantation (p=0.027 and 0.028). CONCLUSION: RA-LV DDD pacemaker implantation is a useful option for patients with symptomatic HOCM.

Improved hypertrophic obstructive cardiomyopathy by left ventricular apex epicardial pacing.

We report a case of severe hypertrophic obstructive cardiomyopahy (HOCM) that was markedly improved by left ventricular (LV) apex epicardial pacing. A 55-year-old woman with HOCM had suffered from dyspnea. Cardiac catheter examination showed a resting pressure gradient across the LV outflow tract of 198 mmHg despite combined medication. During the examination, right dual-chamber pacing could not sufficiently reduce the pressure gradient. Therefore, we treated the patient with LV apex epicardial pacing. The procedure decreased the pressure gradient to 10 mmHg. Clinical symptoms were markedly improved. LV apex epicardial pacing may be an alternative therapy for patients with HOCM who are refractory to other medical treatment.

Anterograde slow pathway is not the same as retrograde slow pathway conducted in the reverse direction in patients with uncommon atrioventricular nodal reentrant tachycardia.

INTRODUCTION: The aim of this study was to examine the location of anterograde and retrograde slow pathways in 16 patients with uncommon atrioventricular nodal reentrant tachycardia (AVNRT), including the fast-slow form in 10, slow-slow form in 5, and both fast-slow and slow-slow forms in 1. METHODS AND RESULTS: Patients were divided into two groups according to the approach used for slow pathway ablation in the initial radiofrequency catheter ablation (RFCA): one approach used earliest atrial activation during tachycardia (ES group, n = 9), and the other used a slow potential during sinus rhythm (SP group, n = 7). When the initial RFCA failed to eliminate slow pathway conduction in the ES group, an additional RFCA guided by a slow potential was performed. The ratio of lengths from the His-bundle region to the RFCA site and coronary sinus ostium (Abl/His-CS ratio) and the ratio of amplitudes of atrial and ventricular potentials at the RFCA site (A/V ratio) were compared between the two groups. In the initial RFCA, retrograde slow pathway conduction was eliminated without impairment of anterograde slow pathway conduction in 8 (89%) patients from the ES group, and bidirectional slow pathway conduction was eliminated in 6 (86%) patients from the SP group. Residual anterograde slow pathway conduction that was preserved after the initial RFCA in 8 of 9 patients was eliminated by an additional slow potential-guided RFCA. Both the Abl/His-CS ratio (0.86 +/- 0.07 vs 0.73 +/- 0.11, P = 0.01) and A/V ratio (0.80 +/- 0.31 vs. 0.14 +/- 0.01, P < 0.001) were higher in the ES group than the SP group. The ratios for the residual anterograde slow pathway ablation in the ES group were similar to those in the SP group. CONCLUSION: The results of this study suggest that the retrograde slow pathway runs more on the atrial side of the tricuspid valve annulus at the level of the coronary sinus ostium compared with the anterograde slow pathway, although both pathways run parallel or are fused in portions more proximal to the His bundle.

Spontaneous regression of focal nodular hyperplasia of the liver.

Focal nodular hyperplasia (FNH) of the liver is a rare benign lesion that probably reflects a local hyperplastic response of hepatocytes to a vascular abnormality. Currently, the natural history of the disease remains largely unknown. We present a patient with FNH of the liver who was followed up for 4 years. A 22-year-old woman with a 3-year history of oral contraceptive use was referred to our hospital in September 1996 for further examination of a liver tumor. A diagnosis of FNH was made using various imaging methods, such as ultrasonography, enhanced computed tomography (CT) scanning, MR imaging, and hepatic angiography, as well as fine-needle biopsy. A decrease in the size of the lesion was observed by enhanced CT scanning during the 4-year observation period. In this patient, oral contraceptive use and its discontinuation may have influenced the natural history of FNH. The present case suggests that an accurate diagnosis is of the utmost importance, and a patient with FNH should be managed conservatively rather than by resection, because FNH has the potential for spontaneous regression with the discontinuation of oral contraceptives.

Prevention of ventricular fibrillation by cilostazol, an oral phosphodiesterase inhibitor, in a patient with Brugada syndrome.

We report the case of 67-year-old man with Brugada syndrome, in whom daily episodes of ventricular fibrillation (VF) occurred every early morning for 4 days. The episodes of VF were completely prevented by an oral administration of cilostazol, a phosphodiesterase inhibitor. This effect was confirmed by the on-and-off challenge test, in which discontinuation of the drug resulted in recurrence of VF and resumption of the drug again prevented VF. This effect may be related to the suppression of I(to) secondary to the increase in heart rate and/or to an increase in Ca2+ current (I(Ca)) due to an elevation of intracellular cyclic AMP concentration via inhibition of phosphodiesterase activity. This drug might have an anti-VF potential in patients with Brugada syndrome.