Refractory Right Ventricular Failure in a Patient with Emery-Dreifuss Muscular Dystrophy.

A 23-year-old man had progressive muscle weakness and Emery-Dreifuss muscular dystrophy (EDMD) due to a LMNA (lamin A/C) mutation. Congestive heart failure diagnosed at 19 years of age. Maximal drug treatment/cardiac resynchronization failed to improve the cardiac function. He was therefore hospitalized due to heart failure. Despite extracorporeal membrane oxygenation, he developed severe right heart dysfunction and died (multiple organ failure). A cardiac lesion's presence determines the prognosis of EDMD. While there are many arrhythmia reports, few reports on heart failure (particularly severe heart failure requiring cardiac transplantation) have been published. Right heart function monitoring and early ventricular-assist device use plus right heart support considering heart transplantation are important.

Arrhythmogenic ß-adrenergic signaling in cardiac hypertrophy: The role of small-conductance calcium-activated potassium channels via activation of CaMKII.

Sustained ventricular arrhythmias (SVAs) lead to sudden cardiac death, for which ß- adrenoreceptor blockers are effective. We hypothesized that electrophysiological changes and arrhythmias by ß- adrenoreceptor stimulation are crucially related to activation of small-conductance calcium-activated potassium (SK) channels via the increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs). The latter served as a model of left ventricular hypertrophy. We performed dual optical mapping of action potentials and Ca2+ transients, and the effects of isoproterenol and apamin, an SK channel blocker, were evaluated in the Langendorff-perfused hearts. Action potential duration was abbreviated by isoproterenol (100 nM) in both WKY rats and SHRs. In contrast, the CaMKII activity was increased by isoproterenol only in SHRs. In the presence of isoproterenol, apamin prolonged the action potential duration only in SHRs (n = 10, from 116.6 ±â€¯5.05 ms to 125.4 ±â€¯3.80 ms, P = 0.011), which was prevented by KN-93, a CaMKII inhibitor. Increase in Ca2+ transients and shortening of Ca2+ transient duration by isoproterenol were similarly observed in both animals, which was not affected by apamin. Apamin reduced the isoproterenol-induced SVAs and maximal slope of action potential duration restitution curve specifically in SHRs. In conclusion, ß- adrenoreceptor stimulation creates arrhythmogenic substrates via the CaMKII-dependent activation of SK channels in cardiac hypertrophy.

Evaluation of the pulmonary artery potential using a 20-polar circumferential catheter and three-dimensional integrated intracardiac echocardiography.

Prolongation of the pulmonary artery potentials (PAPs) in response to short coupling intervals was related to polymorphic QRS configurations during the ventricular tachycardia originating above the pulmonary valve (PA-VT). This prospective study was aimed to investigate the mechanisms of polymorphic changes during the PA-VT. We performed the mapping above the pulmonary valve using a 20-polar circumferential catheter and three-dimensional integrated intracardiac echocardiography in 9 consecutive patients with outflow tract arrhythmias undergoing catheter ablation (UMIN ID: UMIN000021682). The location of successful ablation was right ventricular outflow tract (RVOT) in 6 patients, above the pulmonary valve in 1 patient, left coronary cusp in 1 patient, and unknown in 1 patient. The PAP was detected in six (67%) patients with bipolar voltage of 0.56 ± 0.27 mV. Pacing from bipolar electrodes of the circumferential catheter located above the pulmonary valve captured the PA myocardium only in 1 patient who had the PA-VT (100% in PA-VT vs 0% in non-PA-VT, P = 0.0046), and slight changes of the QRS morphology was observed in accordance with the conduction delay from the stimulus to activation of the RVOT myocardium. The selective PAP capture with conduction delays evoked by bipolar stimulations through a 20-polar circumferential catheter may be a characteristic property of patients with the PA-VT. Conduction delays within the PA and PA-RVOT junction appears to contribute polymorphic QRS changes during the PA-VT.

Long-term reliability of the defibrillator lead inserted by the extrathoracic subclavian puncture.

BACKGROUND: As the transvenous defibrillator lead is fragile and its failure may cause a life-threatening event, reliable insertion techniques are required. While the extrathoracic puncture has been introduced to avoid subclavian crush syndrome, the reports on the long-term defibrillator lead survival using this approach, especially the comparison with the cephalic cutdown (CD), remain scarce. We aimed to evaluate the long-term survival of the transvenous defibrillator lead inserted by the extrathoracic subclavian puncture (ESCP) compared with CD. METHODS: Between 1998 and 2011, 324 consecutive patients who underwent an implantable cardioverter-defibrillator (ICD) implantation in Hokkaido University Hospital were included. ICD leads were inserted by CD from 1998 to 2003 and by contrast venography-guided ESCP thereafter. Lead failure was defined as a nonphysiologic high-rate oversensing with abnormal lead impedance or highly elevated sensing and pacing threshold. RESULTS: Of 324 patients, CD was used in 37 (11%) and ESCP in 287 patients (89%). During the median follow-up of 6.2 years (IQR:3.2-8.3), 7 leads (2 in CD and 5 leads in ESCP group) failed. All patients with lead failure in ESCP group were implanted with either SJM Riata (n = 1) or Medtronic Fidelis lead (n = 4). Five-year lead survival was 93.8% (CI95%:77.3-98.4%) in CD compared with 99.1% (CI95%:96.6-99.8%) in ESCP group (P = 0.903). Univariate Cox regression analysis showed that the use of Fidelis or Riata lead was the strong predictor of the ICD lead failure (HR 13.8, CI95%:2.9-96.5; P = 0.001). CONCLUSIONS: Contrast venography-guided extrathoracic puncture ensures the reliable long-term survival in the transvenous defibrillator leads.

Reentrant atrial tachycardia originating from the sinus venosa region.

A 78-year old woman with palpitation exhibited an atrial tachycardia (AT) of variable cycle lengths resembling atrial fibrillation (AF). Vague centrifugal activation was noted at the sinus venosa region where overdrive pacing demonstrated entrainment with concealed fusion and the stimulus to P wave approximated the electrogram to the P wave interval of 125ms. Application of radiofrequency energy to this site resulted in termination of the AT as well as formation of a fixed block line manifested by the presence of discrete double potentials. These observations indicated the reentrant mechanism of AT originating from the sinus venosa region.

Small-conductance Ca2+-activated K+ channel activation deteriorates hypoxic ventricular arrhythmias via CaMKII in cardiac hypertrophy.

The molecular and electrophysiological mechanisms of acute ischemic ventricular arrhythmias in hypertrophied hearts are not well known. We hypothesized that small-conductance Ca2+-activated K+ (SK) channels are activated during hypoxia via the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) as a model of cardiac hypertrophy. The inhibitory effects of SK channels and ATP-sensitive K+ channels on electrophysiological changes and genesis of arrhythmias during simulated global hypoxia (GH) were evaluated. Hypoxia-induced abbreviation of action potential duration (APD) occurred earlier in ventricles from SHRs versus. WKY rats. Apamin, a SK channel blocker, prevented this abbreviation in SHRs in both the early and delayed phase of GH, whereas in WKY rats only the delayed phase was prevented. In contrast, SHRs were less sensitive to glibenclamide, a ATP-sensitive K+ channel blocker, which inhibited the APD abbreviation in both phases of GH in WKY rats. SK channel blockers (apamin and UCL-1684) reduced the incidence of hypoxia-induced sustained ventricular arrhythmias in SHRs but not in WKY rats. Among three SK channel isoforms, SK2 channels were directly coimmunoprecipitated with CaMKII phosphorylated at Thr286 (p-CaMKII). We conclude that activation of SK channels leads to the APD abbreviation and sustained ventricular arrhythmias during simulated hypoxia, especially in hypertrophied hearts. This mechanism may result from p-CaMKII-bound SK2 channels and reveal new molecular targets to prevent lethal ventricular arrhythmias during acute hypoxia in cardiac hypertrophy. NEW & NOTEWORTHY We now show a new pathophysiological role of small-conductance Ca2+-activated K+ channels, which shorten the action potential duration and induce ventricular arrhythmias during hypoxia. We also demonstrate that small-conductance Ca2+-activated K+ channels interact with phosphorylated Ca2+/calmodulin-dependent protein kinase II at Thr286 in hypertrophied hearts.

Relation between total shock energy and mortality in patients with implantable cardioverter-defibrillator.

BACKGROUND: Implantable Cardioverter-Defibrillator (ICD) shocks have been associated with mortality. However, no study has examined the relation between total shock energy and mortality. The aim of this study is to assess the association of total shock energy with mortality, and to determine the patients who are at risk of this association. METHODS: Data from 316 consecutive patients who underwent initial ICD implantation in our hospital between 2000 and 2011 were retrospectively studied. We collected shock energy for 3 years from the ICD implantation, and determined the relation of shock energy on mortality after adjusting confounding factors. RESULTS: Eighty-seven ICD recipients experienced shock(s) within 3 years from ICD implantation and 43 patients had died during the follow-up. The amount of shock energy was significantly associated with all-cause death [adjusted hazard ratio (HR) 1.26 (per 100 joule increase), p < 0.01] and tended to be associated with cardiac death (adjusted HR 1.30, p = 0.08). The survival rate of patients with high shock energy accumulation (≥182 joule) was lower (p < 0.05), as compared to low shock energy accumulation (<182 joule), likewise to no shock. Besides, the relation between high shock energy accumulation and all-cause death was remarkable in the patients with low left ventricular ejection fraction (LVEF ≤40%) or atrial fibrillation (AF). CONCLUSIONS: Increase of shock energy was related to mortality in ICD recipients. This relation was evident in patients with low LVEF or AF.

Influence of myopotential interference on the Wavelet discrimination algorithm in implantable cardioverter-defibrillator.

BACKGROUND: Wavelet is a morphology-based algorithm for detecting ventricular tachycardia. The electrogram (EGM) source of the Wavelet algorithm is nominally programmed with the Can-RV coil configuration, which records a far-field ventricular potential. Therefore, it may be influenced by myopotential interference. METHODS: We performed a retrospective review of 40 outpatients who had an implantable cardioverter-defibrillator (ICD) with the Wavelet algorithm. The percent-match score of the Wavelet algorithm was measured during the isometric chest press by pressing the palms together. We classified patients with percent-match scores below 70% due to myopotential interference as positive morphology change, and those with 70% or more as negative morphology change. Stored episodes of tachycardia were evaluated during the follow-up. RESULTS: The number of patients in the positive morphology change group was 22 (55%). Amplitude of the Can-RV coil EGM was lower in the positive morphology change group compared to that in the negative group (3.9±1.3 mV vs. 7.4±1.6 mV, P=0.0015). The cut-off value of the Can-RV coil EGM was 5 mV (area under curve, 0.89). Inappropriate detections caused by myopotential interference occurred in two patients (5%) during a mean follow-up period of 49 months, and one of them received an inappropriate ICD shock. These patients had exhibited positive morphology change. CONCLUSIONS: The Wavelet algorithm is influenced by myopotential interference when the Can-RV coil EGM is less than 5 mV.

Characteristics of idiopathic ventricular tachycardia originating above the pulmonary valve.

Panoptic studies of ventricular tachycardia (VT) originating above the pulmonary valve are scarce. The purpose of this study is to clarify the characteristic of idiopathic VT arising above pulmonary valve. We analyzed 15 consecutive patients with idiopathic VT that was successfully abolished by catheter ablation at the right ventricular outflow tract (RVOT-VT, n = 11) and above the pulmonary valve (PA-VT, n = 4). Incidence of syncope was higher in PA-VT than RVOT-VT (100 vs 27 %, P < 0.05) and polymorphic VT was also more prevalent in PA-VT (75 vs 0 %, P < 0.05). The coupling interval (315 ± 29 vs 449 ± 32 ms, mean ± SE) at the onset of VT and minimum cycle length (CL) (192 ± 13 vs 344 ± 37 ms) during VT were shorter in PA-VT (both P < 0.05). Among 12-lead ECG parameters, only R-wave amplitude in lead II was different between groups (2.05 ± 0.17 mV in PA-VT vs 1.44 ± 0.05 mV in RVOT-VT, P < 0.005). At the successful ablation site, the activation time from the onset of QRS complex did not differ between groups (-37 ± 3 vs -31 ± 4, P = 0.405), whereas, the amplitude of intracardiac electrograms was significantly lower in PA-VT (0.83 ± 0.38 mV vs 2.39 ± 0.36 mV, P < 0.05). Although the number of patients in this study is limited, VT originating above the pulmonary valve demonstrated rapid excitation and often degenerated into polymorphic VT, suggesting its malignant electrophysiological characteristics.

Small-conductance Ca2+-activated K+ current is upregulated via the phosphorylation of CaMKII in cardiac hypertrophy from spontaneously hypertensive rats.

Left ventricular hypertrophy is associated with an increased risk of ventricular arrhythmias. However, the underlying molecular basis is poorly understood. It has been reported that small-conductance Ca(2+)-activated K(+) (SK) channels are involved in the pathogenesis of ventricular arrhythmias in heart failure. The present study aimed to test the hypothesis that SK channel activity is increased via the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway in hypertensive cardiac hypertrophy. Normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) were used. Whole cell membrane currents were recorded in isolated ventricular myocytes by the patch-clamp method, and apamin-sensitive K(+) current (IKAS), which is inhibited by apamin (100 nM), an SK channel blocker, was evaluated. IKAS at 40 mV was present in SHRs, whereas it was hardly detectable in WKY rats (0.579 ± 0.046 vs. 0.022 ± 0.062 pA/pF, both n = 6, P < 0.05). IKAS was almost completely abolished by 1 µM KN-93, a CaMKII inhibitor, in SHRs. Optical recordings of left ventricular anterior wall action potentials revealed that apamin prolonged the late phase of repolarization only in SHRs. Western blot analysis of SK channel protein isoforms demonstrated that SK2 was significantly increased in SHRs compared with WKY rats (SK2/GAPDH: 0.66 ± 0.07 vs. 0.40 ± 0.02, both n = 6, P < 0.05), whereas SK1 and SK3 did not differ between groups. In addition, autophosphorylated CaMKII was significantly increased in SHRs (phosphorylated CaMKII/GAPDH: 0.80 ± 0.06 vs. 0.58 ± 0.06, both n = 6, P < 0.05) despite a comparable total amount of CaMKII between groups. In conclusion, SK channels are upregulated via the enhanced activation of CaMKII in cardiac hypertrophy in SHRs.

Predictors and Proarrhythmic Consequences of Inappropriate Implantable Cardioverter-Defibrillator Therapy.

BACKGROUND: Despite the benefits of implantable cardioverter-defibrillator (ICD) therapy, inappropriate shocks can lead to multiple adverse effects. The aim of this study was to clarify the predictors of inappropriate ICD shocks and their proarrhythmic consequences. METHODS AND RESULTS: We retrospectively studied 316 consecutive patients who underwent ICD implantation from December 2000 to December 2011. Of them, 70 (22%) experienced inappropriate ICD shocks without proarrhythmia requiring some intervention; 2 patients (0.6%) had proarrhythmic inappropriate ICD therapy by antitachycardia pacing (ATP), thereby calculated to be 0.18% of patients per year. However, they did not have syncope from this inappropriate ATP. Multivariate analysis identified younger age (≤56 years: hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.02-2.77, P=0.043), paroxysmal atrial fibrillation (HR 3.00, 95% CI 1.64-5.31, P=0.0002), stroke (HR 2.23, 95% CI 1.11-4.47, P=0.024), and no diuretic use (HR 1.72, 95% CI 1.03-2.93, P=0.039) as independent predictors of the occurrence of inappropriate ICD shocks. CONCLUSIONS: Young age, paroxysmal atrial fibrillation, stroke, and no use of diuretics were independently associated with inappropriate ICD shocks. Proarrhythmic inappropriate ICD therapy was observed with an annual incidence of 0.18% by ATP.

Predictors of high defibrillation threshold in patients with implantable cardioverter-defibillator using a transvenous dual-coil lead.

BACKGROUND: Defibrillation testing (DT) is considered a standard procedure during implantable cardioverter-defibrillator (ICD) implantation. However, little is known about the factors that are significantly related to patients with high defibrillation threshold (DFT) using the present triad system. METHODS AND RESULTS: We examined 286 consecutive patients who underwent ICD implantation with a transvenous dual-coil lead and DT from December 2000 to December 2011. We defined patients who required 25 J or more by the implanted device as the high DFT group, and those who required less than 25 J as the normal DFT group. For each patient, assessment parameters included underlying disease, comorbidities, NYHA functional class, drugs, and echocardiographic measures. The high DFT group consisted of 12 patients (4.2%). Multivariate analysis identified 3 independent predictors for high DFT: atrial fibrillation (odds ratio (OR) 4.85, 95% confidence interval (CI) 1.24-22.33, P=0.023), hypertension (OR 4.01, 95% CI 1.08-15.96, P=0.039), thickness of interventricular septum (IVS) >12 mm (OR 4.82, 95% CI 1.17-20.31, P=0.030). CONCLUSIONS: Atrial fibrillation, hypertension and IVS hypertrophy were significantly associated with high DFT. Identification of such patients could help to lower the risk of complications with DT.