Predictors of cardiovascular mortality after an electrical storm in patients with structural heart disease.

BACKGROUND: Electrical storms (ESs) in patients with structural heart disease (SHD) have been reported to be associated with a poor prognosis. However, the detailed cause of death and influence of implantable cardioverter defibrillator (ICD) therapy in ES patients have not been fully investigated. Therefore, we sought to explore the detailed clinical course after an ES and the impact of the ICD therapy in patients with SHDs. METHODS: We retrospectively analyzed 31 consecutive patients with ESs who had undergone an ICD implantation. ESs were defined as three or more ventricular arrhythmias within 24 h. RESULTS: During a mean follow up of 4.5 years, 13 patients died. Among them, cardiovascular death (CVD) was observed in 11/13 (85%), and the leading cause of the CVD was end-stage heart failure. A New York Heart Association class ≥III at the time of the ES occurrence (HR 6.51 95% CI 1.94-25.1, p = 0.003) and any shock therapy (HR 5.94 95% CI 1.06-112.2, p = 0.04) were associated with CVD. CONCLUSION: In the current single center study, the major cause of death in ES patients with SHDs was end-stage heart failure. Any shock therapy was associated with CVD. Arrhythmia management to avoid ICD shocks might reduce the mortality in ES patients.

SK channel blockade prevents hypoxia-induced ventricular arrhythmias through inhibition of Ca2+/voltage uncoupling in hypertrophied hearts.

Ventricular arrhythmia (VA) is the major cause of death in patients with left ventricular (LV) hypertrophy and/or acute ischemia. We hypothesized that apamin, a blocker of small-conductance Ca2+-activated K+ (SK) channels, alters Ca2+ handling and exhibits anti-arrhythmic effects in ventricular myocardium. Spontaneous hypertensive rats were used as a model of LV hypertrophy. A dual optical mapping of membrane potential (Vm) and intracellular calcium (Cai) was performed during global hypoxia (GH) on the Langendorff perfusion system. The majority of pacing-induced VAs during GH were initiated by triggered activities. Pretreatment of apamin (100 nmol/L) significantly inhibited the VA inducibility. Compared with SK channel blockers (apamin and NS8593), non-SK channel blockers (glibenclamide and 4-AP) did not exhibit anti-arrhythmic effects. Apamin prevented not only action potential duration (APD80) shortening (-18.7 [95% confidence interval, -35.2 to -6.05] ms vs. -2.75 [95% CI, -10.45 to 12.65] ms, P = 0.04) but also calcium transient duration (CaTD80) prolongation (14.52 [95% CI, 8.8-20.35] ms vs. 3.85 [95% CI, -3.3 to 12.1] ms, P < 0.01), thereby reducing CaTD80 - APD80, which denotes "Cai/Vm uncoupling" (33.22 [95% CI, 22-48.4] ms vs. 6.6 [95% CI, 0-14.85] ms, P < 0.01). The reduction of Cai/Vm uncoupling was attributable to less prolonged Ca2+ decay constant and suppression of diastolic Cai increase by apamin. The inhibition of VA inducibility and changes in APs/CaTs parameters caused by apamin was negated by the addition of ouabain, an inhibitor of Na+/K+ pump. Apamin attenuates APD shortening, Ca2+ handling abnormalities, and Cai/Vm uncoupling, leading to inhibition of VA occurrence in hypoxic hypertrophied hearts.NEW & NOTEWORTHY We demonstrated that hypoxia-induced ventricular arrhythmias were mainly initiated by Ca2+-loaded triggered activities in hypertrophied hearts. The blockades of small-conductance Ca2+-activated K+ channels, especially "apamin," showed anti-arrhythmic effects by alleviation of not only action potential duration shortening but also Ca2+ handling abnormalities, most notably the "Ca2+/voltage uncoupling."

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.

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.

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.

Cardiac resynchronization therapy in ischemic and non-ischemic cardiomyopathy.

Cardiac resynchronization therapy (CRT) using a biventricular pacing system has been an effective therapeutic strategy in patients with symptomatic heart failure with a reduced left ventricular ejection fraction (LVEF) of 35% or less and a QRS duration of 130 ms or more. The etiology of heart failure can be classified as either ischemic or non-ischemic cardiomyopathy. Ischemic etiology of patients receiving CRT is prevalent predominantly in North America, moderately in Europe, and less so in Japan. CRT reduces mortality similarly in both ischemic and non-ischemic cardiomyopathy, whereas reverse structural left ventricular remodeling occurs more favorably in non-ischemic cardiomyopathy. Because the substrate for ventricular arrhythmias appears to be more severe in cases of ischemic as compared with non-ischemic cardiomyopathy, the use of an implantable cardioverter-defibrillator (ICD) backup method could prolong the long-term survival, especially of patients with ischemic cardiomyopathy, even in the presence of CRT. The aim of this review article is to summarize the effects of CRT on outcomes and the role of ICD backup in ischemic and non-ischemic cardiomyopathy.

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.

Ca2+/calmodulin-dependent protein kinase II increases the susceptibility to the arrhythmogenic action potential alternans in spontaneously hypertensive rats.

Action potential duration alternans (APD-ALT), defined as long-short-long repetitive pattern of APD, potentially leads to lethal ventricular arrhythmia. However, the mechanisms of APD-ALT in the arrhythmogenesis of cardiac hypertrophy remain undetermined. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is known to modulate the function of cardiac sarcoplasmic reticulum and play an important role in Ca(2+) cycling. We thus aimed to determine the role of CaMKII in the increased susceptibility to APD-ALT and arrhythmogenesis in the hypertrophied heart. APD was measured by high-resolution optical mapping in left ventricular (LV) anterior wall from normotensive Wistar-Kyoto (WKY; n = 10) and spontaneously hypertensive rats (SHR; n = 10) during rapid ventricular pacing. APD-ALT was evoked at significantly lower pacing rate in SHR compared with WKY (382 ± 43 vs. 465 ± 45 beats/min, P < 0.01). These changes in APD-ALT in SHR were completely reversed by KN-93 (1 µmol/l; n = 5), an inhibitor of CaMKII, but not its inactive analog, KN-92 (1 µmol/l; n = 5). The magnitude of APD-ALT was also significantly greater in SHR than WKY and was completely normalized by KN-93. Ventricular fibrillation (VF) was induced by rapid pacing more frequently in SHR than in WKY (60 vs. 10%; P < 0.05), which was also abolished by KN-93 (0%, P < 0.05). Western blot analyses indicated that the CaMKII autophosphorylation at Thr287 was significantly increased in SHR compared with WKY. The increased susceptibility to APD-ALT and VF during rapid pacing in hypertrophied heart was prevented by KN-93. CaMKII could be an important mechanism of arrhythmogenesis in cardiac hypertrophy.

Suppression of ventricular fibrillation by electrical modification of the Purkinje system in hypertrophic cardiomyopathy.

A 56-year-old man in hypertrophic cardiomyopathy had an electrical storm caused by ventricular fibrillation (VF). Mapping during the initiation of the VF triggered by a premature ventricular contraction (PVC1), with right bundle branch block (RBBB)-like morphology and superior axis, demonstrated a prominent Purkinje-muscle junction (PMJ) delay at the distal portion of the left posterior fascicle. Delivery of radiofrequency (RF) energy to this area abolished the VF triggered by the PVC1. However, VF emerged by triggering another PVC (PVC2) with RBBB-like morphology and inferior axis. Similarly, the initiation of VF was associated with the PMJ delay at the peripheral left anterior fascicle, where RF delivery completely suppressed the VF. The PMJ delay and subsequent Purkinje-muscle reentry-like activity could be essential for the initiation of the Purkinje-related VF.

Report of the American Heart Association (AHA) Scientific Sessions 2013, Dallas.

The American Heart Association (AHA) Scientific Sessions were held in Dallas on November 16-20, 2013. The meeting is one of the most leading conferences of cardiology in the world, with over 18,000 professional attendees from more than 105 countries. There were 315 invited sessions and 443 abstract sessions, comprising more than 5,000 presentations. The sessions were expanded to 26 program tracks, which included and integrated basic, translational, clinical, and population science. In the series of late-breaking sessions, updates of results from 20 clinical trials were disclosed. Japanese scientists submitted the second most abstracts to the Scientific Sessions in 2013. We appreciate the significant contribution to the sessions by Japanese cardiologists as well as the Japanese Circulation Society.

Strain rate dispersion index can predict changes in left ventricular volume and adverse cardiac events following cardiac resynchronization therapy.

BACKGROUND: We previously reported that the strain rate dispersion index (SRDI), an index of left ventricular (LV) contractility loss because of mechanical dyssynchrony, better predicted the acute response to cardiac resynchronization therapy (CRT) than time-delay indices. However, it remains unclear whether the SRDI can predict the chronic response. Additionally, the SRDI needs to be simplified for use in clinical practice. METHODS AND RESULTS: Echocardiography was performed in 40 heart failure patients who underwent CRT. The SRDI, the average of segmental peak systolic strain rates minus global peak systolic strain rate, was calculated, together with strain-derived time-delay indices (St-SD) in the longitudinal, circumferential and radial directions using a speckle-tracking method. As simplified indices, the longitudinal parameters were calculated from the apical 4-chamber view in addition to 3 apical views. LV end-systolic volume (ESV) significantly decreased 6 months after CRT. Although circumferential St-SD and all SRDIs correlated with the changes in ESV (ΔESV), multivariate analysis revealed that the circumferential SRDI was the single independent determinant of ΔESV. During the 20±14 months after CRT, cardiac events occurred in 14 patients. Kaplan-Meier analyses revealed that all SRDIs were significant predictors of cardiac events whereas none of St-SDs was. CONCLUSIONS: The SRDI predicted the reduction in both LV volume and cardiac events after CRT better than time-delay indices. Additionally, a simplified SRDI could be as good a predictor of CRT response as the original.

Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K(+) channel currents by hypo-osmotic stress in rat ventricular myocytes.

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K(+) channel (KATP) openings by hypo-osmotic stress. The whole-cell KATP currents (IK,ATP) stimulated by 100 µmol/L pinacidil, a K(+) channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and Emax value for pinacidil-activated IK,ATP (measured at 0 mV) was 154 µmol/L and 844 pA, respectively, in normal solution and 16.6 µmol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of IK,ATP during hypo-osmotic stress was attenuated by wortmannin (50 µmol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 µmol/L), an actin filament stabilizer, (ii) the absence of Ca(2+) from the internal and external solutions, and (iii) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the KATP channels. In the single-channel recordings, an inside-out patch was made after approximately 5 min exposure of the myocyte to hypo-osmotic solution. However, the IC50 value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiac IK,ATP through intracellular mechanisms involving the phosphatidylinositol kinase pathway.