"J waves" induced after short coupling intervals: a manifestations of latent depolarization abnormality?

Aims: To confirm the presence of tachycardia-induced slur or notch in the terminal portion of the QRS complexes in a general patient population. Methods and results: A tachycardia-induced J wave was defined as a slur or notch in the terminal portion of the QRS complexes newly induced at short RR intervals during atrial premature contractions (APCs) or atrial electrical stimulation in the electrophysiological study (EPS). Twenty-three out of 2000 patients with general diseases were involved. All patients with aborted sudden cardiac death, ventricular fibrillation or a family history of sudden cardiac death were excluded. The mean age was 72 ± 9 years, and 11 patients were male (47.8%). When the RR interval was shortened from 821 ± 142 ms to 464 ± 52 ms in the conducted APCs (P < 0.0001), J waves became diagnostic (0.02 ± 0.03 mV to 0.20 ± 0.07 mV, P < 0.0001). J waves were confined to the inferior leads in 22 (95.7%) patients and were notched in 11 (47.8%) and slurred in 12 (52.2%) patients. The induction of J waves was accompanied by visible changes of the QRS morphology. When the post-APC RR interval was prolonged to 992 ± 305 ms (P = 0.0154 vs. baseline), the J waves were similar to baseline levels. During the EPS, J wave induction was confirmed during atrial stimulation. There were no characteristic clinical or ECG features in the patients with tachycardia-induced J waves. Conclusions: J waves can be newly induced by short RR intervals in a general patient population, and a conduction delay is the likely mechanism causing such J waves.

Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

The neuroradiological findings and its outcomes of intracerebral hemorrhage (ICH) were compared between the non-vitamin K antagonist oral anticoagulant (NOAC) therapy and warfarin therapy. In the latest 3 years, 13 cases of nonvalvular atrial fibrillation on NOAC therapy were admitted for ICH. For comparison, 65 age- and gender-comparable patients with ICH on warfarin therapy were recruited. Three NOACs had been prescribed: dabigatran (n = 4), rivaroxaban (n = 2), and apixaban (n = 7). The average ages were 76 ± 9 and 78 ± 8 years in the warfarin (n = 65) and NOAC groups (n = 13), respectively. There was no difference in the clinical features, including the CHADS2 score or HAS-BLED score: 2.62 ± 1.31 versus 2.62 ± 1.33, or 1.09 ± 0.43 versus 1.00 ± 0.41, for the warfarin and NOAC groups, respectively. The volume of ICH <30 ml was found in 84.6% of the patients on NOACs, but it was found in 53.8% of the patients on warfarin (p = 0.0106). The expansion of hematoma was limited to 7 patients (10.8%) of the warfarin group. A lower hospital mortality and better modified Rankin Scale were observed in the NOAC group than in the warfarin group: 1 (7.7%) versus 27 (41.5%; p = 0.0105) and 3.2 ± 1.4 versus 4.5 ± 1.6 (p = 0.0057), respectively. In conclusion, ICH on NOAC therapy had smaller volume of hematoma with reduced rate of expansion and decreased mortality compared with its occurrence on warfarin.

Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force-frequency relationship and enhanced poststimulation potentiation.

Mechanical alternans (MA) is frequently observed in patients with heart failure, and is a predictor of cardiac events. However, there have been controversies regarding the conditions and mechanisms of MA. To clarify heart rate-dependent contractile properties related to MA, we performed incremental right atrial pacing in 17 idiopathic dilated cardiomyopathy (DCM) patients and in six control patients. The maximal increase in left ventricular dP/dt during pacing-induced tachycardia was assessed as the force gain in the force-frequency relationship (FG-FFR), and the maximal increase in left ventricular dP/dt of the first post-pacing beats was examined as the force gain in poststimulation potentiation (FG-PSP). As a result, MA was induced in 9 DCM patients (DCM MA(+)) but not in the other 8 DCM patients (DCM MA(-)), and not in any of the control patients. DCM MA(+) had significantly lower FG-FFR (34.7 ± 40.9 vs 159.4 ± 103.9 mmHg/s, P = 0.0091) and higher FG-PSP (500.0 ± 96.8 vs 321.9 ± 94.9 mmHg/s, P = 0.0017), and accordingly a wider gap between FG-PSP and FG-FFR (465.3 ± 119.4 vs 162.5 ± 123.6 mmHg/s, P = 0.0001) than DCM MA(-) patients. These characteristics of DCM MA(+) showed clear contrasts to those of the control patients. In conclusion, MA is caused with an impaired force-frequency relationship despite significant poststimulation potentiation, suggesting that MA reflects ineffective utilization of the potentiated intrinsic force during tachycardia.

Relationship between electroanatomical voltage mapping characteristics and breakout site of ventricular activation in idiopathic ventricular tachyarrhythmia originating from the right ventricular outflow tract septum.

OBJECTIVE: To assess the electrophysiological characteristics of the breakout site of ventricular activation using electroanatomical voltage mapping (EVM) and its relation to the optimal ablation site in idiopathic ventricular tachyarrhythmias originating from the outflow tract of the (RVOT) septum. METHODS: Twenty-eight patients with symptomatic drug-refractory premature ventricular complexes (PVCs) and/or ventricular tachycardia (VT) originating from the RVOT septum and 5 control subjects with WPW syndrome were included. Low-voltage areas (LVAs) were defined as signal amplitudes between 0.1 and 1.5 mV. The borderline between the normal area and the LVA was defined as "border," and the distance from the LVA to the border (length of LVA) was measured. RESULTS: In all 28 patients and control subjects, there was an LVA below the pulmonary valve. There was no significant difference in length of LVA between patients with idiopathic ventricular arrhythmias and control subjects (2.0 ± 0.6 vs. 1.9 ± 0.1 cm). In 19 of the 28 patients, the optimal ablation site was identical to the border area. In all 11 patients who had pre-potentials at the successful ablation site, there were two cases with polymorphic VT and/or ventricular fibrillation associated with PVCs. In these two cases, length of LVA was longer than in other patients (4.0 and 3.9 cm vs. 1.8 ± 0.5 cm (n = 26)), and the optimal ablation site was located at the border area. CONCLUSION: The border area, including the LVA, tends to be the breakout site and/or origin of ventricular arrhythmias in idiopathic ventricular tachyarrhythmia originating from the RVOT septum.

An appropriate defibrillation threshold obtained by the combined connection between two shock leads and ICD generator.

A 60-year-old man with arrhythmogenic right ventricular cardiomyopathy was readmitted for the battery exchange of his implantable cardioverter-defibrillator (ICD). Since (i) he had been treated with a dual-coil shock lead (Sprint Fidelis, Medtronic) and (ii) pre-operative venography showed mild collateral flow to the left subclavian vein, a single-coil lead was additionally implanted. However, the single-coil defibrillation system was unable to terminate the induced ventricular fibrillation (VF), thus dual defibrillation shock pathways were created using the connection to the superior vena cava coil of the Fidelis lead. The combined connections of the two shock leads provided an appropriate margin of the defibrillation threshold.

Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization.

BACKGROUND: Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear. METHODS AND RESULTS: This study included 50 patients (44 men; age, 45 ± 17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels. CONCLUSIONS: We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.

The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis.

Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T-cells secreting inflammatory cytokines. In this study, rat models of EAM were prepared by injection with porcine cardiac myosin. One week after immunization, edaravone was administered intraperitoneally at 3 or 10 mg/kg/day to rats for 2 weeks. Cardiac function was measured by haemodynamic and echocardiographic studies and TUNEL assay was performed. Left ventricular (LV) expression of NADPH oxidase sub-units (p47(phox) and p67(phox)), pro-inflammatory cytokines (TNF-alpha), endoplasmic reticulum (ER) stress signalling proteins (GRP78, caspase-12 and GADD153) and mitogen-activated protein kinase (MAPK) family proteins (phospho-p38 MAPK and phospho-JNK) were measured by western blotting. Edaravone improved LV function in a dose-dependent manner. Central venous pressure was significantly low and LV ejection fraction and fractional shortening was significantly high in edaravone groups compared with those in the vehicle group. In addition, edaravone treatment down-regulated LV expressions of p47(phox), TNF-alpha, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67(phox), GRP78, caspase-12 and TUNEL-positive cells of rats with EAM treated with edaravone were significantly low compared with those of the vehicle group. These findings suggest that edaravone ameliorated the progression of EAM by inhibiting oxidative and ER stress and, subsequently, cardiac apoptosis.

Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog.

BACKGROUND: Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I(Kr) blocker, E-4031, each administered to five open-chest dogs. METHODS: We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation-recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid-myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation. RESULTS: Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E-4031, bepridil caused mild, reverse use-dependent changes in ventricular repolarization, and less ARI dispersion than E-4031 during slow ventricular pacing. Both drugs increased ARI(max) and cycle length at 50% of ARI(max), though the changes were smaller after bepridil than after E-4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E-4031 versus no dog treated with bepridil. CONCLUSIONS: Unlike the pure I(kr) blocker, E-4031, bepridil exhibited weak properties of reverse use-dependency and protected against sympathetic stimulation-induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator.

Consumption of green and roasted teas and the risk of stroke incidence: results from the Tokamachi-Nakasato cohort study in Japan.

BACKGROUND: and purpose Green tea consumption is inversely associated with death from stroke. The purpose of the present study was to assess whether it is inversely associated with subsequent stroke incidence and whether this association is preserved even with roasted tea leaves. METHODS: In 1998, 6358 Japanese adults (2087 men and 4271 women) aged 40-89 years without a history of stroke or heart disease completed a lifestyle questionnaire, including consumption of green tea or roasted tea. By the end of 2003, 110 stroke events (59 cerebral infarction events, 34 cerebral haemorrhage events, 15 subarachnoidal haemorrhage events and two stroke events of unspecified subtype) had been documented. Cox proportional hazards regression analysis was used to calculate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for total stroke events, cerebral infarction events and cerebral haemorrhage events according to consumption categories of green tea and roasted tea. RESULTS: A considerably lower risk was observed for total stroke incidence in both the middle (multivariable HR, 0.43; 95% CI, 0.25-0.74; P = 0.002) and the high (multivariable HR, 0.41; 95% CI, 0.24-0.70; P = 0.001) categories of green tea consumption. This inverse association was consistent even when cerebral infarction and cerebral haemorrhage were analysed separately. The consumption of roasted tea was not associated with stroke risk. CONCLUSIONS: Green tea consumption is associated with a reduced risk of total stroke incidence, cerebral infarction and cerebral haemorrhage.

Non-pharmacological management of ventricular tachycardia.

Ventricular tachyarrhythmias (VTA), a major cause of sudden cardiac death, require meticulous management in order to prevent recurrent episodes. Recently, non-pharmacological interventions, including radiofrequency catheter ablation and implantable cardioverter defibrillators (ICD), have become important treatments of VTA. Catheter ablation is curative in a relatively high percentage of patients presenting with idiopathic monomorphic ventricular tachycardia (VT). For VT associated with structural heart disease, however, the efficacy of catheter ablation remains limited, and ICD is the first-line therapy. In a subset of patients presenting with recurrent episodes of ventricular fibrillation (VF), catheter ablation is a therapeutic option when the VF is triggered by specific premature ventricular complexes. In Japan, unlike in the United States and Europe, ICD have not yet been accepted as first-line prevention of sudden cardiac death caused by VTA. The efficacy of ICD is occasionally limited by intolerable complications, such as electrical storm, inappropriate shock delivery and infection. Catheter ablation and ICD therapy might need to be combined for problematic cases.

Comparison of conduction delay in the right ventricular outflow tract between Brugada syndrome and right ventricular cardiomyopathy: investigation of signal average ECG in the precordial leads.

BACKGROUND: In both Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC), electrical abnormalities in the right ventricular outflow tract (RVOT) are important for arrhythmogenesis. OBJECTIVES: The aim of this study was to compare conduction delay in the right ventricular in BS with that in ARVC using the signal-averaged electrocardiogram. METHODS: Twenty patients with BS (18 men and 2 women; 55 +/- 12 years old; 9 symptomatic and 11 asymptomatic) and eight patients with ARVC (six men and two women; 53 +/- 16 years old) were included. We assessed the presence of late potentials (LPs) and the filtered QRS duration (fQRSd) in V(2) and V(5) using a high-pass filter of 40 Hz (fQRSd:40) and 100 Hz (fQRSd:100). RESULTS: In ARVC, there was no significant difference in fQRSd:40 between V2 and V5 (158 +/- 19 vs. 145 +/- 17 ms, respectively): however, in BS, fQRSd:40 in V2 was significantly longer than fQRSd:40 in V5 (147 +/- 15 vs. 125 +/- 10 ms, P < 0.001). In ARVC, there was no significant difference between fQRSd:40 and fQRSd:100 in V(2) and V(5) (158 +/- 19 vs. 142 +/- 23 ms and 145 +/- 17 vs. 132 +/- 9 ms, respectively). In contrast, in BS, fQRSd:100 was significantly shorter than fQRSd:40 in V2 (110 +/- 8 ms vs. 147 +/- 15, P < 0.001). The relative decrease in fQRSd:100 compared with fQRSd:40 in V2 was significantly greater in BS than in ARVC. CONCLUSION: The dominant prolongation of the fQRSd in the right precordial lead in BS was different from the characteristics of ARVC, which may be caused by the conduction delay due to fibro-fatty replacement in RV.

Incidence and initial characteristics of pilsicainide-induced ventricular arrhythmias in patients with Brugada syndrome.

BACKGROUND: In patients with Brugada syndrome, class I antiarrhythmic drugs can trigger ventricular arrhythmias (VA). The incidence and initial characteristics of VA that developed after pilsicainide was examined in 28 patients with Brugada-type electrocardiographic (ECG) abnormalities and with a positive response in the pilsicainide test. The clinical outcome was also compared between patients with and without pilsicainide-induced VA. METHODS AND RESULTS: In all patients, pilsicainide increased ST segment elevation and accentuated type 1 ECG changes. Ventricular tachycardia (VT) developed in 3 patients and premature ventricular complexes (PVC) in 2 other patients. These 5 patients (group I) had higher ST segment elevation in lead V2 on the ECG at baseline and after pilsicainide and showed a longer QTc interval after pilsicainide than the other 23 patients (group II). However, there was no difference between the 2 groups regarding incidence of prior cardiac events, results of signal-averaged ECG, HV interval, inducibility of ventricular fibrillation by programmed electrical stimulation, or QRS duration. In 1 patient, PVC originated from 3 sites, 2 of which triggered polymorphic VT. The right ventricular (RV) outflow tract was the origin of 2 types of PVC, and other RV sites of 5 other types. During a 45 +/- 37 months follow-up, polymorphic VT recurred in 2 patients in group II. CONCLUSIONS: Pilsicainide induced VA in some patients with Brugada syndrome, but this result may not be used as a parameter of the risk stratification of Brugada syndrome. Multiple PVC induced by pilsicainide and triggering polymorphic VT originated from several RV sites is an important factor when considering patients for treatment with catheter ablation.

Distinct U wave changes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).

Although catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with fatal ventricular arrhythmias and sudden death, the ECG findings are not fully understood. In this paper, we report on alterations in the U-wave. Seven patients from 6 families with CPVT in which bidirectional tachycardia and polymorphic VT were induced by exercise or isoproterenol infusion visited our hospitals. VT was not inducible by programmed electrical stimulation. A novel gene mutation of the ryanodine receptor 2 (RyR2) was confirmed in 2 families. In one of these patients, U-wave alternans was observed following ventricular pacing at 160 beats/min. In the other patient, U-wave alternans was observed during the recovery phase after the exercise stress test, which was terminated because of polymorphic VT. In both cases, leads V3-V5 were the leads showing alternans most clearly. In the third patient, a negative U-wave became positive following a pause from sinus arrest and a change in T-wave was also noted. Since such findings were not found in the other subjects who underwent electrophysiologic study, isoproterenol infusion or exercise stress testing, the phenomenon seems to be relevant to the underlying pathogenesis of CPVT. The genesis and significance of U-wave alteration need to be determined.

Comparative effects of pranidipine with amlodipine in rats with heart failure.

The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and +/-dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-alpha, and improved sarcoplasmic reticulum Ca2+ ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.

A case-control pilot study on n-3 polyunsaturated fatty acid as a negative risk factor for myocardial infarction.

The relation between n-3 polyunsaturated fatty acid (PUFA) and nonfatal myocardial infarction is still controversial. A multicenter case-control pilot study on n-3 PUFA as a negative risk factor for myocardial infarction was performed in Niigata prefecture. Seventy-three patients with acute myocardial infarction (AMI) and age and gender matched controls (n = 84) were recruited. Serum leptin levels were significantly higher in patients with AMI than the controls (8.1 +/- 6.7 ng/mL versus 5.8 +/- 3.7 ng/mL, P < 0.01), and serum high-density lipoprotein cholesterol (HDLc) levels were significantly lower in patients with AMI than the controls (46 +/- 10.5 mg/dL versus 60 +/- 15 mg/dL, P < 0.00001). Statistically significant differences were preserved in leptin and HDLc when the data were analyzed separately by gender. Serum levels (%weight) of linolenic acid (C18:3:n3), eicosapentaenoic acid (C20:5:n3), docosapentaenoic acid (C22:5:n3), and total n-3 PUFA were significantly lower in patients with AMI than the control group (P < 0.000001, < 0.05, < 0.05, < 0.05, respectively). The serum n-3 PUFA/saturated fatty acid (SF) ratio and n-3 PUFA/n-9 monounsaturated fatty acid (MUFA) ratio were significantly lower in patients with AMI than the controls (P < 0.05 and < 0.01, respectively). When the subjects were separated into two categories according to an n-3/n-6 PUFA ratio below 0.3 or above 0.3, patients with AMI were more frequently in the former while the controls were more frequently in the latter (P < 0.05). N-3 PUFA may be a negative risk factor for AMI. The results suggest leptin is a risk factor for AMI irrespective of ethnicity and gender.

High-dose cyclophosphamide as an effective therapy for a patient with refractory multiple myeloma relapsing after autologous stem cell transplantation.

Alkylating agents are often used to treat patients with multiple myeloma (MM). However, it is not common for high-dose cyclophosphamide (CPM) therapy to be used as a treatment for MM. Herein, we report a case of refractory MM associated with hypercalcemia. We decided to give her high-dose CPM. After this treatment, the serum calcium level decreased and the tumor mass in the iliac bone was reduced. This therapy is potentially useful for patients with refractory MM.

Electrophysiologic study-guided therapy with sotalol for life-threatening ventricular tachyarrhythmias.

The aim of this study was to investigate the long-term efficacy and safety of electrophysiologic study (EPS)-guided sotalol administration combined with implantable cardioverter defibrillators (ICD) for ventricular tachyarrhythmias (VTA). This study enrolled 92 patients with both structural heart disease and sustained VTA. Sotalol was administered to 57 patients, and its efficacy was assessed by EPS. Long-term treatment was continued in combination with ICD in 31 patients (57%) whose VTA was no longer inducible (responder group) and in 16 patients whose VTA remained inducible (nonresponder group). The long-term outcomes were compared among the responder group, the nonresponder group, and 35 ICD recipients untreated with antiarrhythmic drugs (ICD-only group). During a mean follow-up of 44 +/- 33 months, the recurrence of VTA was not significantly different between all patients treated with sotalol (30%) and patients in the ICD-only group (46%). However, the recurrence of VTA was significantly lower in the responder (13%) than in the nonresponder (63%) or the ICD-only groups (46%). There was no significant difference in VTA recurrence between the nonresponder and the ICD-only groups. One patient each in the responder and the ICD-only groups died suddenly, and all-cause mortality was similar in the three groups. The incidence of inappropriate ICD discharges was less in the sotalol than in the ICD-only groups. No patient had to discontinue long-term sotalol treatment because of the adverse effects. In conclusion, sotalol reduced VTA recurrence in the responding patients and inappropriate ICD discharge. EPS may predict the efficacy of sotalol for VTA recurrence.

Unsuccessful internal defibrillation in Brugada syndrome: focus on refractoriness and ventricular fibrillation cycle length.

INTRODUCTION: In patients with Brugada syndrome, implantable cardioverter defibrillator (ICD) is the only reliable treatment to prevent sudden death though, in some cases, internal defibrillation may be unsuccessful. The aim of this study was to examine the determinants of defibrillation failure, with a focus on electrophysiologic characteristics. METHODS: The study included 51 patients treated with ICD: 22 with Brugada syndrome and 29 with structural heart disease (SHD). The prevalence of defibrillation energy requirement precluding the programming of a 10-J safety margin, the mean right ventricular effective refractory period (ERP), and mean induced ventricular fibrillation cycle length (VFCL) from the stored ICD electrograms, were compared between the two patient groups. RESULTS: High defibrillation requirements were observed in 18% of patients with Brugada syndrome versus 0% of patients with SHD. However, the patients with SHD had larger heart size than those with Brugada syndrome. Mean VFCL and mean ERP were both significantly shorter in patients with Brugada syndrome than in patients with SHD, and ERP and VFCL were significantly correlated. CONCLUSION: Patients with Brugada syndrome have a high prevalence of high defibrillation energy requirement, and short ventricular ERP and VFCL.

Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan.

OBJECTIVES: We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS). BACKGROUND: The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms. METHODS: Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes. RESULTS: Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p < 0.005). CONCLUSIONS: In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations.