Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Risk stratification in asymptomatic patients with Brugada syndrome: Utility of multiple risk factor combination rather than programmed electrical stimulation.

BACKGROUND: The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. Asymptomatic BrS patients generally have a better prognosis than those with symptoms. The purpose of this study was to evaluate the value of nonaggressive PES with up to two extra stimuli and predict clinical factors for risk stratification in asymptomatic BrS patients. METHODS: The study enrolled 193 consecutive asymptomatic BrS patients with type 1 ECG (mean age: 50 ± 13 years, 180 males) who underwent PES using a nonaggressive uniform protocol. Cardiac events (CEs: sudden cardiac death or ventricular tachyarrhythmia) during the follow-up period were examined. RESULTS: During a mean follow-up of 101 ± 48 months, seven asymptomatic patients (3.6%) had a CE. The incidence of CEs was not different between patients with and without inducible ventricular tachyarrhythmia by PES (p = .51). The clinical significance of risk factor combinations, including spontaneous type 1 ECG, family history of sudden cardiac death, QRS duration in lead V2 , and presence of J wave, was evaluated. Using the Kaplan-Meier method according to the number of risk factors, the prevalence of CE in patients with three or four risk factors was determined to be significantly higher than in those with one risk factor (p = .02 and p = .004, respectively). CONCLUSIONS: The present study suggests that inducibility of ventricular tachyarrhythmia does not predict future CEs in asymptomatic BrS patients. Combination analysis of the other four clinical risk parameters may be effective for risk assessment.

The coronary artery calcium score correlates with left atrial low-voltage area: Sex differences.

INTRODUCTION: In patients with coronary artery disease, a high coronary artery calcium score (CACS) correlates with atrial fibrillation (AF); however, the association between left atrial (LA) remodeling progression and coronary arteriosclerosis is unclear. This study aimed to evaluate the relationship between LA remodeling progression and the CACS. METHODS: This retrospective study enrolled 148 patients with AF (paroxysmal AF, n = 94) who underwent catheter ablation. Voltage mapping for the left atrium and coronary computed tomography for CACS calculations were performed. The ratio of the LA low-voltage area (LA-LVA), defined by values less than 0.5 mV divided by the total LA surface without pulmonary veins, was calculated. Patients with LA-LVA (<0.5 mV) >5% and ≤5% were classified as the LVA (n = 30) and non-LVA (n = 118) groups, respectively. Patient characteristics and CACS values were compared between the two groups. RESULTS: LA volume, age, CHA2 DS2 VASc score, and percentage of female patients were significantly higher, and the estimated glomerular filtration rate was lower in the LVA group than in the non-LVA group. The CACS was significantly higher in the LVA group (248.4 vs. 13.2; p = .001). Multivariate analysis identified the LA volume index and CACS as independent predictors of LA-LVA (<0.5 mV) greater than 5%. The areas under the receiver operating characteristic curves for predicting LA-LVA (<0.5 mV) greater than 5% with CACS were 0.695 in the entire population, 0.782 in men, and 0.587 in women. CONCLUSION: Progression of LA remodeling and coronary artery calcification may occur in parallel. A high CACS may indicate advanced LA remodeling, especially in men.

Long-term prognosis in patients with non-type 1 Brugada electrocardiogram: Results from a large Japanese cohort of idiopathic ventricular fibrillation.

BACKGROUND: Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with spontaneous, drug-induced, or fever-induced type 1 morphology. Prognosis in type 2 or 3 Brugada electrocardiogram (Br-ECG) patients remains unknown. The purpose of this study is to evaluate long-term prognosis in non-type 1 Br-ECG patients in a large Japanese cohort of idiopathic ventricular fibrillation (The Japan Idiopathic Ventricular Fibrillation Study [J-IVFS]). METHODS: From 567 patients with Br-ECG in J-IVFS, a total of 28 consecutive non-type 1 patients who underwent programmed electrical stimulation (PES) (median age: 58 years, all male, previous sustained ventricular tachyarrhythmias [VTs] 1, syncope 11, asymptomatic 16) were enrolled. Cardiac events (CEs: sudden cardiac death or sustained VT/ventricular fibrillation) during the follow-up period were examined. RESULTS: During a median follow-up of 136 months, four patients (14%) had CEs. None of patients with PES- have experienced CEs. There was no statistically significant clinical risk factor for the development of CEs. Using the Kaplan-Meier method, the event-free rate significantly decreased in a group with all 3 risk factors (symptom, wide QRS complex in lead V2 , and positive PES) (p = .01). CONCLUSIONS: Our study revealed long-term prognosis in patients with non-type 1 Br-ECG. The combination analysis of these risk factors may be useful for the risk stratification of CEs in non-type 1 Br-ECG patients. The present study suggests that the patients with all these parameters showed high risk for CEs and need to be carefully followed.

Quality of life improvements by durable pulmonary vein isolation in patients with atrial fibrillation.

INTRODUCTION: Successful pulmonary vein isolation (PVI) can improve the quality of life (QOL) of patients with atrial fibrillation (AF). However, the role of durable PVI for such QOL improvement is not known. The aim of this study was to clarify the effectiveness of durable PVI in improving the QOL of patients with AF. METHODS AND RESULTS: We assessed 119 patients who underwent PVI (age 66.4 ± 9.6 years, 104 paroxysmal AF). A scheduled electrophysiological study was performed 6 months after the first PVI session-regardless of recurrence of AF-to assess the durability of PVI and to identify and re-isolate reconnected pulmonary veins. QOL scores were evaluated by an AF-specific QOL questionnaire and checked at baseline, 6 months, and 1 year after the first session. In patients without AF recurrence (nonrecurrence group, n = 93), the scores at 6 months improved compared with those at baseline; conversely, the scores did not improve in patients with AF recurrence (n = 26). Nevertheless, the scores at 1 year improved compared with those at 6 months in both groups. Within the nonrecurrence group, the score difference between 6 months and baseline was higher in the durable PVI group (n = 58) than that in the nondurable PVI group (n = 35). CONCLUSIONS: The QOL of AF patients improved by the resumption of sinus rhythm following PVI. Patients with durable PVI had increased QOL scores compared with those with nondurable PVI. The durability of PVI may achieve further improvements in the QOL of patients with AF.

Comparison of touch-up ablation rate and pulmonary vein isolation durability between hot balloon and cryoballoon.

INTRODUCTION: This study aimed to compare touch-up ablation (TUA) rates and pulmonary vein isolation (PVI) durability of hot balloon ablation (HBA) and cryoballoon ablation (CBA) in paroxysmal atrial fibrillation (PAF) patients. METHODS: In total, 137 PAF patients were enrolled in the study. Among them, 59 underwent two HBA procedures at 6-month intervals and 78 patients underwent two CBA sessions, both regardless of atrial fibrillation recurrence. Propensity score matching was performed to estimate similar patient characteristics between the HBA and CBA groups. RESULTS: Each group comprised of 46 matched patients for comparison. The TUA rate at the first session was higher for HBA (49 of 184 PVs) than for CBA (20 PVs) (P = .01), with the highest incidence at the left superior pulmonary vein (LSPV). The rates of PVI durability at the second session performed 7 months later were similar between HBA (168 of 184 PVs) and CBA (162 PVs) groups. The PVI durability rate at the TUA sites of the first session was higher for HBA than for CBA (41 of 49 PVs vs 10 PVs, respectively; P = .01). Fifty percent of the patients underwent HBA at 73°C for the LSPV. HBA performed at 73°C yielded a lower TUA rate than that at 70°C (16 of 23 PVs vs 7 of 23 PVs; P = .008). CONCLUSIONS: While PVI durability was similar between HBA and CBA, the TUA rate was higher for HBA than for CBA, especially on the LSPV. For LSPV, HBA at a balloon temperature of 73°C may reduce the TUA rate.

Characteristics of ventricular intracardiac electrograms of ventricular tachycardias originating from the epicardia in patients with an implantable cardioverter defibrillator.

INTRODUCTION: While characteristic waveforms of 12-lead electrocardiograms have been reported to predict the epicardial origin of ventricular tachycardia (VT), it has not been fully examined whether ventricular intracardiac electrograms (VEGMs) recorded from the implantable cardioverter defibrillator (ICD) via telemetry can determine the origin of VT or not. The aim of this study was to investigate the VEGM characteristics of VT originating from the epicardia. METHOD AND RESULTS: Intracardiac VEGMs of the induced VTs, with detected sites of origin during the VT study, were recorded in 15 (23 VTs) of the 46 patients. The characteristics of the 23 VTs were evaluated using far-field and near-field VEGMs recorded via telemetry. Five of 23 VTs were found to be focused on the epicardial site (epi group) and 18 VTs were focused on the endocardium (endo group). VTs of the epi group had longer VEGM duration in far-field EGM than those of the endo group (epi group: 240 ± 49 ms vs endo group: 153 ± 45 ms; P = 0.002) and the duration from the onset to the peak of VEGM was also longer than that of the endo group (epi group: 153 ± 53 ms vs endo group: 63 ± 28 ms; P < 0.001). There was no difference in the V wave duration in tip-ring EGM between both groups (epi group: 122 ± 52 ms vs endo group: 98 ± 6 ms; P = 0.377). CONCLUSION: Evaluation of intracardiac VEGM before VT ablation may be helpful to predict the epicardial origin of VT in patients with an ICD.

Usefulness of epicardial impedance evaluation for epicardial mapping and determination of epicardial ablation site for ventricular tachycardia: A pilot study.

BACKGROUND: During epicardial mapping, determination of appropriate ablation sites in low voltage areas (LVA) is challenging because of large epicardial areas covered by adipose tissue. OBJECTIVE: To evaluate the impedance difference between epicardial fat and the epicardial LVA using multiple detector computed tomography (MDCT). METHODS: We enrolled patients who underwent ventricular tachycardia (VT) ablation via the epicardial approach after endocardial ablation failure. After the procedure, MDCT-derived images of epicardial fat were loaded to the mapping system. Then, all points acquired during sinus rhythm were retrospectively superimposed and analyzed. RESULTS: This study included data from 7 patients (62.5 ± 3.9 years old) who underwent eight epicardial VT ablation procedures. After the procedure, MDCT-derived images of epicardial fat were registered in eight procedures. Retrospective analysis of 1,595 mapping and 236 ablation points was performed. Of the 1,595 mapping points on the merged electroanatomical and epicardial fat maps, normal voltage area (NVA) and low voltage area (LVA) without fat had lower impedance than those with fat (NVA without fat 182 ± 46 Ω vs. NVA with fat 321 ± 164.0 Ω, P  =  0.001, LVA without fat 164 ± 69 Ω vs. LVA with fat 248 ± 89 Ω, P  =  0.002). Of the 236 ablation points, initial impedance before ablation was higher on epicardial fat than on epicardial LVA without fat (134 ± 16 Ω vs. 156 ± 28 Ω, P  =  0.01). CONCLUSIONS: Real time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites and avoid adipose tissue. However, the number of patients in the present study is limited. Further investigation with a large number of patients is needed to confirm our result.

The prognostic impact of single extra-stimulus on programmed ventricular stimulation in Brugada patients without previous cardiac arrest: multi-centre study in Japan.

Aims: The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. One of the reasons for discrepant results may be due to the selection of stimulation protocol. We evaluated the prognostic value of a positive PES result (PES+) according to the inducible pacing sites and the number of extra-stimuli in BrS patients without previous cardiac arrest (CA). Methods and results: We enrolled 224 consecutive BrS patients without previous CA (mean age 51 ± 14 years, 209 males), who underwent PES with the identical protocol. Clinical outcomes of development of CA were explored in the patients with and without PES+ according to sites and number of extra-stimuli. During a mean follow-up period of 76 months, 12 cardiac events (CE: sudden cardiac death or documented VF) occurred (8 with and 4 without PES+). The incidence of CE was not different in patients with and without PES+, those with PES+ from RVA (n = 72) or RVOT (n = 60), and those with and without PES+ by up to 2 extra-stimuli (n = 58). However, in patients that were PES+ by a single extra-stimulus (n = 8) the incidence of CE was significantly higher than in those without PES+ (8.8 vs. 0.6%/year, P < 0.0001). On univariate analysis, syncope, spontaneous type 1 ECG, and PES+ by a single extra-stimulus were associated with CE. Conclusion: Details of the stimulation protocol may be important for risk assessment in BrS patients without previous CA. A single extra-stimulus may be useful in stratifying risk in patients with spontaneous type 1 ECG and syncope.

Life-Threatening Ventricular Arrhythmia and Brugada-Type ST-Segment Elevation Associated With Acute Ischemia of the Right Ventricular Outflow Tract.

BACKGROUND: Brugada-type ECG (Br-ECG) is occasionally observed during acute myocardial ischemia of the right ventricular outflow tract (RVOT). No studies have explored, however, the association of ventricular tachyarrhythmia and development of Br-ECG due to acute ischemia of the RVOT.Methods and Results:The study included 13 consecutive patients with acute ischemia of the RVOT during coronary catheterization. Patients were divided into 2 groups: those with Br-ECG (group B) and those without (group N). The proportion of male patients was higher in group B than in group N (100% vs. 25%, P<0.01), and VT/VF developed in only patients with Br-ECG (group B). In group B, VT/VF was observed in patients without pre-existing organic change in the conus/right ventricular (RV) branch of the right coronary artery and no VT/VF was seen in patients with organic coronary stenosis despite Br-ECG. CONCLUSIONS: Acute myocardial ischemia of the RVOT caused Br-ECG predominantly in male patients and subsequent development of VT/VF in some patients. VT/VF was seen in patients without any obstructive lesion but arrhythmic events were not observed in RVOT ischemia in the case of pre-existing coronary occlusion or stenosis of the conus or RV branch, suggesting the effects of precondition.

Early repolarization pattern and its day-to-day dynamic change as markers for ventricular fibrillation in patients with vasospastic angina.

AIMS: An early repolarization (ER) pattern is a risk factor for ventricular fibrillation (VF) in certain diseases. However, it is unclear whether this association holds for patients with vasospastic angina (VSA). Moreover, the reported long-term follow-up of implantable cardioverter defibrillator (ICD) therapy for VSA patients is limited to 3 years. This study aimed to clarify the relation between ER and VF in patients with VSA and to investigate the long-term outcomes of ICD therapy. METHODS AND RESULTS: This retrospective, observational survey evaluated 265 consecutive VSA patients, including 21 with VF. Their electrocardiogram findings and clinical course were analysed over a mean follow-up of 5.5 ± 3.3 years. Early repolarization was observed in 64 patients (24.2%) and was more frequent in patients with VF history than those without (P = 0.001). Early repolarization was independently associated with VF history. During follow-up, four patients had VF recurrences. Ventricular fibrillation recurrence was higher in patients with ER (log-rank, P = 0.018) or VF history (log-rank, P < 0.001) than those without. Among patients with ER, day-to-day variations in ER (P = 0.003) and notching of ER pattern (P = 0.03) were associated with VF history. Cases with day-to-day variation showed a higher incidence of VF recurrence during follow-up (log-rank, P = 0.007). During long-term follow-up, 23.5% of patients with an ICD received appropriate shock therapy. CONCLUSION: The presence of ER, especially with day-to-day variation, can help predict VF recurrence in VSA patients. Implantable cardioverter defibrillator implantation is a reasonable approach for the secondary prevention of VF in high-risk VSA patients.

Transient sinus node dysfunction following sinus node artery occlusion due to radiofrequency catheter ablation of the septal superior vena cava-right atrium junction.

We performed catheter ablation to septal superior vena cava (SVC)-right atrium (RA) junction rapid firing in a 57-year-old man with paroxysmal atrial fibrillation. He later experienced transient sinus node dysfunction resulting from injury to the sinus node artery (SNA), which branched only from the proximal region of the left circumflex artery. The direction of the SNA should be considered during catheter ablation at the septal SVC-RA junction, especially if the sinus node is supplied by only one SNA from the right coronary artery or the left circumflex artery.

Unmasking Brugada-type electrocardiogram on deep inspiration.

BACKGROUND: Electrocardiogram (ECG) recorded at the upper intercostal lead positions is recommended as an additional diagnostic clue for Brugada syndrome (BrS), but similar recording conditions to unmask ECG signs have not been explored. METHODS AND RESULTS: We evaluated the diagnostic usefulness for unmasking ECG signs of BrS using recordings at the upper intercostal lead position, on deep inspiration and on standing. In 34 patients (mean age, 49±14 years; 30 male) with diagnosed and suspected BrS, ECG type and ST-elevation in leads V1-V3 recorded at a higher position by 1 rib from the standard position (3ICS), and at standard lead positions (4ICS) on deep inspiration (DI test) and on standing (Stand test) were compared with the conventional lead positions (baseline). While type 1 ECG had been documented in 17 of 34 patients on at least 1 occasion in the past, only 4 had the sign at baseline during the study. Twenty patients had type 1 on 3ICS recording, 18 on DI test, and 6 on Stand test. Among 17 patients without previous documentation of spontaneous type 1, 7 had type 1 on 3ICS recording, 6 on DI test, and 1 on Stand test. CONCLUSIONS: ECG recording on deep inspiration is useful to unmask diagnostic signs of BrS and has similar accuracy to 3ICS recording.

J wave and fragmented QRS formation during the hyperacute phase in Takotsubo cardiomyopathy.

BACKGROUND: The J wave and fragmented QRS (fQRS) on electrocardiography are suggested to be closely related to cardiac arrhythmogenesis. Takotsubo cardiomyopathy (TTC) occasionally causes fatal cardiac conditions including life-threatening ventricular arrhythmia. There has been, however, only 1 case report describing the J wave in TTC, and fQRS has not been reported thus far in relation to clinical courses and prognosis. METHODS AND RESULTS: J wave and fQRS formation were investigated in 31 consecutive patients with TTC. Nine patients (29%) had J waves and/or fQRS (group A), whereas the remaining 22 did not (group B). The J wave (4 patients), fQRS (4 patients), or both (1 patient) appeared transiently during the hyperacute phase. Left ventricular ejection fraction was significantly lower in group A. Summed defect score of single-photon emission computed tomography using iodine 123 beta-methyl-p-iodophenyl-pentadecanoic acid, and creatine kinase MB isozyme (CKMB) were significantly higher in group A. On multivariate analysis CKMB was a significant indicator of J wave or fQRS. Moreover, the J wave was a significant indicator for cardiac death and/or ventricular tachyarrhythmia (odds ratio, 11.5; P=0.026). CONCLUSIONS: Patients with TTC frequently had J waves and/or fQRS during the hyperacute phase, and which were associated with myocardial damage. J wave was also an indicator for cardiac death and/or ventricular tachyarrhythmia. J waves and fQRS may be useful markers for myocardial damage.

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan part 3: Inappropriate internal processing in the automatic diagnosis of electrocardiograms and its problems.

Computer diagnosis of electrocardiograms is widely used to provide useful information in clinical practice and medical checkups. However, it is common for users to be confused by the inappropriate diagnosis. We illustrate some examples of inappropriate automatic diagnoses and discuss the actual situation of inappropriate automatic processing and its problems.

New clinical and electrocardiographic classification in patients with idiopathic ventricular fibrillation.

INTRODUCTION: The presence of early repolarization (ER) recently has been considered as a prognostic marker for sudden cardiac death in patients with idiopathic ventricular fibrillation (IVF), but there are certain numbers of IVF patients lacking ER. We aimed to clarify the clinical and electrocardiographic characteristics of the patients with IVF in the presence and absence of ER. METHODS AND RESULTS: We studied 64 consecutive IVF patients from the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS) registry, which subjected with at least one episode of documented VF in the absence of structural heart diseases and excluding Brugada syndrome. We assessed clinical and electrophysiological characteristics in the IVF patients with and without ER. ER was defined as J-point elevation of >0.1 mV in either inferior or lateral leads. Twelve-lead electrocardiogram (ECG) demonstrated 24 (38%) of 64 patients with ER (ER[+] group) and the remaining 40 (62%) patients without ER (ER[-] group ). ER[+] group had a male predominance (92% for males) and ER[-] group revealed nearly equal distribution in both sexes. While no patients in ER[+] group showed intraventricular conduction disturbance (CD) with abnormal axis deviation and/or bundle branch block in ECG, 9 in ER[-] group had signs of CD (ER[-]/CD[+] subgroup). ER[-]/CD[+] subgroup had prolonged P-R interval and QRS duration compared to other patient groups. CONCLUSION: We found 3 distinct ECG patterns in IVF patients. In addition to the presence and absence of ER, there is a subgroup without ER demonstrating intraventricular CD, which represents a distinct clinical entity of IVF.

Macroreentrant atrial tachycardia in patients without previous atrial surgery or catheter ablation: clinical and electrophysiological characteristics of scar-related left atrial anterior wall reentry.

INTRODUCTION: Macroreentrant atrial tachycardia (MRAT) has been described most frequently in patients with prior cardiac surgery. Left atrial tachycardia and flutter are common in patients who undergo atrial fibrillation ablation; however, few reports describe left atrial MRAT involving the regions of spontaneous scarring. Here, we describe left atrial MRAT in patients without prior cardiac surgery or catheter ablation (CA) and discuss the clinical and electrophysiological characteristics of tachycardia and outcome of CA. METHODS AND RESULTS: An electrophysiological study and CA were performed in 6 patients (3 men; age 76 ± 6 years) with MRAT originating from the left atrial anterior wall (LAAW). No patient had a history of cardiac surgery or CA in the left atrium. Spontaneous scars (areas with bipolar voltage ≤ 0.05 mV) were observed in all patients. The activation map showed a figure-eight circuit with loops around the mitral annulus (4 counterclockwise and 2 clockwise) and a low-voltage area with LAAW scarring. The mean tachycardia cycle length was 303 ± 49 milliseconds. The conduction velocity was significantly slower in the isthmus between the scar in the LAAW and the mitral annulus than in the lateral mitral annulus (0.17 ± 0.05 m/s vs 0.94 ± 0.35 m/s; P = 0.003). Successful ablation of the isthmus caused interruption of the tachycardia and rendered it noninducible in all patients. CONCLUSION: Spontaneous LAAW scarring is an unusual cause of MRAT, showing activation patterns with a figure-eight configuration. Radiofrequency CA is a feasible and effective treatment in such cases.

Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability.

RATIONALE: The human ether-a-go-go-related gene (hERG) encodes the α subunit of the potassium current I(Kr). It is highly expressed in cardiomyocytes and its mutations cause long QT syndrome type 2. Heat shock protein (Hsp)70 is known to promote maturation of hERG. Hsp70 and heat shock cognate (Hsc70) 70 has been suggested to play a similar function. However, Hsc70 has recently been reported to counteract Hsp70. OBJECTIVE: We investigated whether Hsc70 counteracts Hsp70 in the control of wild-type and mutant hERG stability. METHODS AND RESULTS: Coexpression of Hsp70 with hERG in HEK293 cells suppressed hERG ubiquitination and increased the levels of both immature and mature forms of hERG. Immunocytochemistry revealed increased levels of hERG in the endoplasmic reticulum and on the cell surface. Electrophysiological studies showed increased I(Kr). All these effects of Hsp70 were abolished by Hsc70 coexpression. Heat shock treatment of HL-1 mouse cardiomyocytes induced endogenous Hsp70, switched mouse ERG associated with Hsc70 to Hsp70, increased I(Kr), and shortened action potential duration. Channels with disease-causing missense mutations in intracellular domains had a higher binding capacity to Hsc70 than wild-type channels and channels with mutations in the pore region. Knockdown of Hsc70 by small interfering RNA or heat shock prevented degradation of mutant hERG proteins with mutations in intracellular domains. CONCLUSIONS: These results indicate reciprocal control of hERG stability by Hsp70 and Hsc70. Hsc70 is a potential target in the treatment of LQT2 resulting from missense hERG mutations.

Prevalence and electrophysiological characteristics of typical atrial flutter in patients with atrial fibrillation and chronic obstructive pulmonary disease.

AIMS: Chronic obstructive pulmonary disease (COPD) is one of the important underlying diseases of atrial fibrillation (AF). However, the prevalence and electrophysiological characteristics of typical atrial flutter (AFL) in patients with AF and COPD remain unknown. The purpose of the present study was to investigate those characteristics. METHODS AND RESULTS: We investigated 181 consecutive patients who underwent catheter ablation of AF. Twenty-eight patients were diagnosed with COPD according to the Global Initiatives for Chronic Obstructive Lung Disease (GOLD) criteria. Forty patients with no lung disease served as a control group. We analysed the electrophysiological characteristics in these groups. Typical AFL was more common in the COPD group (19/28, 68%) than in the non-COPD group (13/40, 33%; P = 0.006). The prevalence of AFL increased with the severity of COPD: 4 (50%) of 8 patients with GOLD1, 13 (72%) of 18 patients with GOLD2, and 2 (100%) of 2 patients with GOLD3. Atrial flutter cycle length and conduction time from the coronary sinus (CS) ostium to the low lateral right atrium (RA) during CS ostium pacing before and after the cavotricuspid isthmus ablation were significantly longer in the COPD group than in the non-COPD group (285 vs. 236, 71 vs. 53, 164 vs. 134 ms; P = 0.009, 0.03, 0.002, respectively). CONCLUSION: In COPD patients with AF, conduction time of RA was prolonged and typical AFL was commonly observed.