Electrophysiological evidence of right atrial epicardial connections in a case with recurrent common atrial flutter.

The majority of the cavotricuspid isthmus (CTI) region consists of discretely arranged muscle bundles separated by connective tissue. Heterogeneity in the anatomic arrangement of the muscle bundles results in differences in the endocardial and epicardial activation patterns. We present a case of recurrent atrial flutter (AFL) despite the presence of a complete endocardial CTI block. We found epicardial-endocardial breakthrough (EEB) sites on the right atrial high septum. In addition, the epicardial excitation confirmed by endocardial activation mapping was detected as far-field potentials. Radiofrequency ablation was performed at the EEB site. No AFL has recurred for 12 months after the present procedure.

Significance of mitral L-waves in predicting late recurrences of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: The mitral L-wave, a prominent mid-diastolic filling wave in echocardiographic examinations, is associated with severe left ventricular diastolic dysfunction. The relationship between the mitral L-wave and outcome of catheter ablation (CA) in patients with atrial fibrillation (AF) has not been established. This study aimed to evaluate the predictive value of mitral L-waves on AF recurrence after CA. METHODS: This was a retrospective and observational study in a single center. One hundred forty-six patients (mean age; 63.9 [56.0-72.0] years, 71.9% male) including 66 non-paroxysmal AF patients (45.2%) who received a first CA were enrolled. The mitral L-waves were defined as a distinct mid-diastolic flow velocity with a peak velocity ≥20 cm/s following the E wave in the echocardiographic examinations before CA. The patients enrolled were divided into groups with (n = 31, 21.2%) and without (n = 115, 78.8%) mitral L-waves. Univariate and multivariate analyses were carried out to determine the predictive factors of late recurrences of AF (LRAFs), which meant AF recurrence later than 3 months after the CA. RESULTS: During a follow-up of 28.8 (15.0-35.8) months, the ratio of LRAFs in patients with mitral L-waves was significantly higher than that in those without mitral L-waves (15 [46.9%] vs. 16 [14.0%], p < .001). A multivariate analysis using a Cox proportional hazard model revealed that the mitral L-waves were a significant predictive factor of LRAFs (hazard ratio: 3.09, 95% confidence interval: 1.53-6.24, p = .002). CONCLUSION: The appearance of mitral L-waves could predict LRAFs after CA.

Association between the COVID-19 pandemic in 2020 and out-of-hospital cardiac arrest outcomes and bystander resuscitation efforts for working-age individuals in Japan: a nationwide observational and epidemiological analysis.

BACKGROUND: Improving out-of-hospital cardiac arrest (OHCA) prognosis within the working-age population is important, but no studies have investigated the effects of COVID-19 pandemic specifically on the working-age population with OHCAs. We aimed to determine the association between the 2020 COVID-19 pandemic and OHCA outcomes and bystander resuscitation efforts among the working-age population. METHODS: Prospectively collected nationwide, population-based records concerning 166 538 working-age individuals (men, 20-68 years; women, 20-62 years) with OHCA between 2017 and 2020 were assessed. We compared characteristics and outcome differences of the arrests between three prepandemic years (2017-2019) and the pandemic year 2020. The primary outcome was neurologically favourable 1-month survival (cerebral performance category 1 or 2). Secondary outcomes were bystander cardiopulmonary resuscitation (BCPR), dispatcher-assisted instruction for cardiopulmonary resuscitation (DAI-CPR), bystander-provided defibrillation (public access defibrillation (PAD)) and 1-month survival. We examined variations in bystander resuscitation efforts and outcomes among pandemic phase and regional classifications. RESULTS: Among 149 300 OHCA cases, 1-month survival (2020, 11.2%; 2017-2019, 11.1% (crude OR (cOR) 1.00, 95% CI 0.97 to 1.05)) and 1-month neurologically favourable survival (7.3%-7.3% (cOR 1.00, 95% CI 0.96 to 1.05)) were unchanged; however, the neurologically favourable 1-month survival rate decreased in 12 of the most COVID-19-affected prefectures (7.2%-7.8% (cOR 0.90, 95% CI 0.85 to 0.96)), whereas it increased in 35 other prefectures (7.5%-6.6% (cOR 1.15, 95% CI 1.07 to 1.23)). Favourable outcomes decreased for OHCAs of presumed cardiac aetiology (10.3%-10.9% (cOR 0.94, 95% CI 0.90 to 0.99)) but increased for OHCAs of non-cardiac aetiology (2.5%-2.0% (cOR 1.27, 95% CI 1.12 to 1.44)). BCPR provision increased from 50.7% of arrests prepandemic to 52.3% (crude OR 1.07, 95% CI 1.04 to 1.09). Compared with 2017-2019, home-based OHCAs in 2020 increased (64.8% vs 62.3% (crude OR 1.12, 95% CI 1.09 to 1.14)), along with DAI-CPR attempts (59.5% vs 56.6% (cOR 1.13, 95% CI 1.10 to 1.15)) and multiple calls to determine a destination hospital (16.4% vs 14.5% (cOR 1.16, 95% CI 1.12 to 1.20)). PAD use decreased from 4.0% to 3.7% but only during the state of emergency period (7 April-24 May 2020) and in prefectures significantly affected by COVID-19. CONCLUSIONS: Reviewing automated external defibrillator (AED) locations and increasing BCPR through DAI-CPR may help prevent pandemic-associated decreases in survival rates for patients with cardiac OHCAs.

The inducibility and focus of atrial fibrillation after ablation in patients with tachycardia-induced heart failure.

BACKGROUND: The inducibility of atrial fibrillation (AF) and incidence of nonpulmonary vein (nonPV) triggers in patients with heart failure (HF) have not been elucidated. Furthermore, the relationship between AF triggers and the change in the left ventricular (LV) function after catheter ablation (CA) remains unclear. METHODS: A total of 101 consecutive patients with a history of HF due to tachycardia who underwent CA of AF were prospectively enrolled (64.8 ± 10.7 years, male 72.3%, and paroxysmal AF 15.8%). According to the AF inducibility by isoproterenol (ISP), the patients were divided into two groups: inducible AF (66.3%) and noninducible AF (33.7%). Furthermore, inducible AF was categorized into a PV type (61.2%) and nonPV type (38.8%). This study investigated the AF recurrence and change in the LV ejection fraction (LVEF) after CA. RESULTS: AF recurred in 35 patients (34.7%) during the follow-up period (41.6 ± 26.8 months). Kaplan-Meier curves showed that patients with noninducible AF had just as bad an AF recurrence rate as those with the nonPV type. Cox proportional hazards models also revealed that noninducible AF (Hazard-ratio, 5.74; 95% CI, 1.81-18.13) was associated with a higher risk of recurrence. The LVEF significantly improved after the CA (from 49.1 ± 16.3% to 67.0 ± 7.9%). However, the nonPV type was associated with a lower improvement in the LVEF (Odds-ratio, 0.18; 95% CI, 0.05-0.70). CONCLUSION: The AF inducibility was associated with AF recurrence. Furthermore, the nonPV triggers were associated with a lesser improvement in the LVEF. Confirming the AF inducibility and triggers was important to predict the outcome after CA.

Role of Intracardiac Defibrillation During the Ablation Procedure as a Predictor of Atrial Fibrillation Recurrence After Catheter Ablation.

Intracardiac defibrillation (IDF) is performed to restore sinus rhythm (SR) during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). This study aimed to investigate the change in the IDF threshold before and after RFCA during the ablation procedure and determine whether the IDF threshold after RFCA was associated with the AF substrate and AF recurrence. A total of 141 consecutive patients with drug-refractory persistent AF (age 62.5 ± 10.3 years, 84.4% male) were enrolled in this study. Before RFCA, we initially performed IDF with an output of 1 J. When IDF failed to restore SR, the output was gradually increased to 30 J. After RFCA, we attempted pacing-induced AF to provoke other focuses of AF. When AF was induced, we performed IDF again to terminate AF with outputs of 1 to 30 J. The change in the IDF threshold to restore SR before and after RFCA was evaluated. After RFCA, the IDF threshold for restoring SR significantly decreased (from 11.5 ± 8.6 J to 4.0 ± 3.8 J, P < 0.001). During the follow-up (24.3 ± 12.2 months), SR was maintained in 107 patients (75.9%). The multivariate analysis using a Cox proportional-hazards model revealed that an IDF threshold of > 5 J after RFCA was significantly associated with the AF recurrence (HR, 3.99; 95% confidence interval 1.93-8.22; P = 0.0001). RFCA decreased the IDF threshold for restoring SR in patients with persistent AF. The IDF output of > 5 J after RFCA could be a predictor of AF recurrence independent of the AF substrate.

Comparison of the Transdermal Bisoprolol Patch with Oral Bisoprolol Fumarate Administration as a Therapeutic Agent for Idiopathic Frequent Premature Ventricular Contractions.

The transdermal bisoprolol patch (TB) was designed to maintain a sustained concentration of bisoprolol in plasma by a higher trough concentration than oral bisoporolol (OB). We compared the efficacy between TB and OB in patients with idiopathic premature ventricular contractions (PVCs) while considering their duration of action.A total of 78 patients with a PVC count of ≥ 3,000 beats/24 hours were divided into groups treated with TB 4 mg (n = 43) or OB 2.5 mg (n = 35). PVCs were divided into positive heart rate (HR) -dependent PVCs (P-PVCs) and non-positive HR-dependent PVCs (NP-PVCs) based on the relationship between the hourly PVC density and hourly mean HR. Twenty-four-hour Holter electrocardiograms were performed before and 1 to 3 months after the initiation of therapy.There were no significant between-group differences in the baseline characteristics. Both the TB (from 14.6 [9.9-19.2] to 7.6 [1.7-15.8]%, P < 0.001) and OB (from 13.2 [7.6-21.9] to 4.6 [0.5-17.0]%, P = 0.0041) significantly decreased the PVC density, and there was no significant difference between the two groups (P = 0.73). Compared to OB, the TB had similar effects in reducing the PVC density for P-PVCs (P = 0.96), and NP-PVCs (P = 0.71). The TB significantly decreased the P-PVC density from baseline not only during day-time (P < 0.001) but also night-time (P = 0.0017), while the OB did not significantly decrease the P-PVC density from baseline during night-time (P = 0.17).Compared to OB, the TB could be used with the same efficacy of reducing idiopathic PVCs. The TB may be a more useful therapeutic agent than OB for P-PVCs during a 24-hour period.

Clinical Factors Associated with a Successful Catheter Ablation Outcome in Elderly Patients with Atrial Fibrillation.

Catheter ablation is currently an established treatment for symptomatic paroxysmal atrial fibrillation (AF). We focused on elderly patients with a high prevalence of AF and attempted to identify the clinical factors associated with unsuccessful ablation outcomes.Among 735 consecutive patients who underwent AF ablation procedures, 108 (14.7%, 66 men) aged ≥ 75 years were included. Of them, 80 had paroxysmal AF, and the remaining 28 non-paroxysmal AF. All patients underwent pulmonary vein (PV) isolation and occasionally additional ablation. When AF recurred, redo ablation procedures were performed if the patient so desired.The mean number of ablation procedures was 1.1 ± 0.4 times per patient. During a mean follow-up of 38.7 ± 21.7 months, sinus rhythm was maintained in 100 patients (92.6%) without any antiarrhythmic drugs, but not in the remaining 8 (7.4%). Left atrial diameter (LAD, P < 0.001), left ventricular (LV) systolic diameter (P < 0.001), LV diastolic diameter (P = 0.001), non-PV AF foci (P = 0.036), and diabetes (P = 0.045) were associated with unsuccessful ablation procedures. Multivariate logistic regression analysis revealed a large LAD and non-PV AF foci were significant independent predictors of AF recurrences, with odds ratios of 0.76 (P = 0.019) and 0.04 (P = 0.023), respectively. In a total of 124 procedures, one major (0.8%) and 11 minor (8.9%) complications occurred.In elderly AF patients, catheter ablation of AF is effective and safe. Non-PV AF foci and a large LAD were independent clinical predictors of unsuccessful AF ablation outcomes.

The relationship between serum indoxyl sulfate and the renal function after catheter ablation of atrial fibrillation in patients with mild renal dysfunction.

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces renal disorders and atrial fibrillation (AF). It is well known that renal dysfunction is a risk factor for AF and radiofrequency catheter ablation (RFCA) improves the renal function. However, the improvement in the renal function after RFCA in patients with early stage chronic kidney disease (CKD) and the serial changes in the IS level have not been fully elucidated. This study aimed to investigate whether IS affects the improvement in the renal function. A total of 91 consecutive patients with mild kidney dysfunction (CKD stage I-II) who underwent RFCA and maintained sinus rhythm were prospectively enrolled. The plasma IS level and estimated glomerular filtration rate (eGFR) were determined before, 3 months, and 1 year after RFCA. The patients were divided according to the IS quartiles (Q1-4; < 0.4, 0.4-0.7, 0.7-1.2, and > 1.2 µg/ml). There was no significant difference in the eGFR among the IS quartiles. A significantly higher eGFR improvement rate was obtained for IS-Q4 than the other quartiles (p = 0.039). The IS-Q4 IS level significantly decreased at 1 year after RFCA (1.8 ± 0.8 to 1.2 ± 0.7 µg/ml, p < 0.01). The multivariable logistic model revealed that a high-IS level (IS-Q4) was an independent predictor of an eGFR improvement (OR 3.33; 95% CI 1.16-9.59; p = 0.026). A high-IS level reduction after RFCA improved the renal function in AF patients with mild kidney dysfunction.

Impact of Atrial Fibrillation Triggers on Long-Term Outcomes of a Second Catheter Ablation of Nonparoxysmal Atrial Fibrillation.

Background: Catheter ablation (CA) of atrial fibrillation (AF) triggers, including non-pulmonary vein (PV) foci, contributes to improved procedural outcomes. However, the clinical significance of an AF trigger ablation during second CA procedures for nonparoxysmal AF is unknown. Methods and Results: We enrolled 94 patients with nonparoxysmal AF undergoing a second CA. Intracardiac cardioversion during AF using high-dose isoproterenol was performed to determine the presence or absence of AF triggers. PV re-isolations were performed if PV potentials recurred, and if AF triggers appeared from any non-PV sites, additional ablation was added to those sites. We investigated the incidence of atrial arrhythmia recurrence (AAR) >3 months post-CA. Of the 94 enrolled patients, AF triggers were identified in 65 (69.1%), and of those with AF triggers, successful elimination of the triggers was achieved in 47 patients (72.3%). Multivariate analysis revealed that no observed AF triggers were a significant predictor of AAR (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.21-3.46, P=0.019). In a subanalysis of the patients with AF triggers, multivariate analysis showed that unsuccessful trigger ablation was significantly associated with AAR (HR 5.84, 95% CI 2.79-12.22, P<0.01). Conclusions: Having no observed AF triggers during a second CA session significantly increased the risk of AAR, as did unsuccessful CA of AF triggers.

Effects of the 2020 COVID-19 pandemic on outcomes of out-of-hospital cardiac arrest and bystander resuscitation efforts: a nationwide cohort study in Japan.

Background and importance There is limited knowledge about the nationwide impact of the 2020 COVID-19 pandemic in Japan on out-of -hospital cardiac arrest (OHCA) outcomes.Objectives The aim of this study was to investigate the impact of the 2020 COVID-19 pandemic on OHCA outcomes and bystander resuscitation efforts in Japan. Design Retrospective analysis of a nationwide population-based registry of OHCA cases. Settings and participants To conduct this study, we created a comprehensive database comprising 821 665 OHCA cases by combining and reconciling the OHCA database for 835 197 OHCA cases between 2017 and 2020 with another database, including location and time records. After applying exclusion and inclusion criteria, we analysed 751 617 cases.Outcome measures and analysis The primary outcome measure for this study was survival with neurologically favourable outcome (cerebral performance category 1 or 2). We compare OHCA characteristics and outcomes between prepandemic and pandemic years, and also investigated differences in factors associated with outcomes. Results We found that survival with neurologically favourable outcome and the rates of bystander cardiopulmonary resuscitation (CPR) slightly increased in the pandemic year [2.8% vs. 2.9%; crude odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03-1.10; 54.1% vs. 55.3%, 1.05 (1.04-1.06), respectively], although the incidence of public access defibrillation (PAD) slightly decreased [1.8% vs. 1.6%, 0.89 (0.86-0.93)]. Calls for hospital selection by emergency medical service (EMS) increased during the pandemic. Subgroup analysis showed that the incidence of neurologically favourable outcome increased in 2020 for OHCA cases that occurred on nonstate of emergency days, in unaffected prefectures, with noncardiac cause, nonshockable initial rhythm, and during daytime hours. Conclusions During the 2020 COVID-19 pandemic in Japan, survival with neurologically favourable outcome of OHCA patients and bystander CPR rate did not negatively change, despite the decrement in PAD incidence. However, these effects varied with the state of emergency, region, and characteristics of OHCA, suggesting an imbalance between medical demand and supply, and raising concerns about the pandemic.

Impact of the COVID-19 pandemic on prehospital characteristics and outcomes of out-of-hospital cardiac arrest among the elderly in Japan: A nationwide study.

Aim: To assess the impact of the 2020 coronavirus disease (COVID-19) pandemic on the prehospital characteristics and outcomes of out-of-hospital cardiac arrest (OHCA) in the elderly. Methods: In this population-based nationwide observational study in Japan, 563,100 emergency medical service-unwitnessed OHCAs in elderly (≥65 years) patients involving any prehospital resuscitation efforts were analysed (144,756, 140,741, 140,610, and 136,993 cases in 2020, 2019, 2018, and 2017, respectively). The epidemiology, characteristics, and outcomes associated with OHCAs in elderly patients were compared between 3 years pre-pandemic (2017-2019) and the pandemic year (2020). The primary outcome was neurologically favourable one-month survival. The secondary outcomes were the rate of bystander cardiopulmonary resuscitation (CPR), defibrillation by a bystander, dispatcher-assisted (DA)-CPR attempts, and one-month survival. Results: During the pandemic year, the rates of neurologically favourable 1-month survival (crude odds ratio, 95% confidence interval: 1.19, 1.14-1.25), bystander CPR (1.04, 1.03-1.06), and DA-CPR attempts (1.10, 1.08-1.11) increased, whereas the incidence of public access defibrillation (0.88, 0.83-0.93) decreased. Subgroup analyses based on interaction tests showed that the increased rate of neurologically favourable survival during the pandemic year was enhanced in OHCA at care facilities (1.51, 1.36-1.68) and diminished or abolished on state-of-emergency days (0.90, 0.74-1.09), in the mainly affected prefectures (1.08, 1.01-1.15), and in cases with shockable initial rhythms (1.03, 0.96-1.12). Conclusions: The COVID-19 pandemic increased the bystander CPR rate in association with enhanced DA-CPR attempts and improved the outcomes of elderly patients with OHCAs.

A case of constrictive pericarditis with a milk of calcium pericardial effusion undergoing surgical treatment.

Milk of calcium (MOC) pericardial effusion (PE) is extremely rare and has rarely been reported. A 78-year-old man was referred to our institution because of breathlessness and bilateral leg edema. Echocardiography revealed mild PE. In addition, abrupt posterior motion of the ventricular septum in early diastole was observed. A non-contrast chest computed tomography revealed a hyperdense PE, with Hounsfield units of 130, suggestive of MOC PE. Right heart catheterization (RHC) revealed that the right ventricular pressure had a dip and plateau pattern. We diagnosed the patient with constrictive pericarditis (CP) with MOC PE. As the right heart failure secondary to CP was refractory to medical therapy, we decided to perform surgical treatment. During pericardiectomy, a highly viscous PE, of which the color was pale and reddish brown, was aspirated. Chemical analysis of the PE revealed a very high calcium content of 39.2 mmol/L. The clinical symptoms secondary to CP improved. RHC performed postoperatively confirmed the disappearance of a dip and plateau pattern in the right ventricular pressure. In conclusion, we experienced a of CP with MOC PE and surgical treatment contributed to the improvement of the clinical symptoms and pericardial constriction secondary to CP. Learning objective: Because constrictive pericarditis (CP) with milk of calcium (MOC) pericardial effusion (PE) can cause severe morbidity and even mortality, the early diagnosis of CP is important in patients suspected of having MOC PE. MOC PE has hyperdensity on computed tomography, so its findings could be helpful in the diagnosis of MOC PE. Pericardiectomy for CP with MOC PE may contribute to the improvement of the clinical symptoms and pericardial constriction secondary to CP.

Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity.

BACKGROUND: Dealing with chemotherapy-related cardiac dysfunction (CTRCD) remains a significant problem complicated by the difficulty in early detection of cardiotoxicity. Electrocardiogram (ECG) is expected to be the most realistic methodology due to lower cost-performance and non-invasiveness. We investigated the long-term visual fluctuations in the ECG waveforms in patients with chronic doxorubicin (DOX)-induced cardiotoxicity to identify ECG indices for the early detection of cardiotoxicity. METHODS: We conducted a retrospective case series study by reviewing the medical records of 470 consecutive patients with malignant lymphoma who were treated with DOX at our institute between January 2010 and December 2017. Of them, 23 (4.9%) patients developed left ventricular dysfunction and were diagnosed with CTRCD using echocardiography. We assessed the ECG indices on 12-lead ECG recordings before and after treatment in 15 patients; eight patients were excluded due to conduction disturbances or atrial fibrillation. RESULTS: CTRCD was detected at a median of 475 (interquartile range, IQR: 341-1333) days after initiating chemotherapy. The evaluation of ECG indices preceding CTRCD development was performed 93 (IQR: 52-232) days before the detection of CTRCD. In the stage of CTRCD, the most significant ECG change was T-wave flattening in leads V3-V6 (12 patients, 80%). Additionally, QTa prolongation was observed in leads I and aVL (n = 10, 66%), leads II, III, and aVF (n = 9, 60%), and leads V3-V6 (n = 10, 73%). These ECG changes were not observed before the treatment but were detected mildly in the pre-CTRCD stage, which subsequently worsened in the CTRCD stage. CONCLUSIONS: This study indicated that T-wave changes and QTa prolongation may be useful as an early indicator before the onset of CTRCD in patients with DOX-induced cardiotoxicity.

Evaluation of oral anticoagulants in atrial fibrillation patients over 80 years of age with nonsevere frailty.

BACKGROUND: The safety and efficacy of an oral anticoagulant (OAC) treatment and the difference between direct OACs (DOACs) and warfarin in nonsevere frail elderly patients with AF are unclear. METHODS: This was a retrospective and observational study of 354 patients over 80 years of age with nonsevere frailty who were diagnosed with AF and treated with OACs. Nonsevere frailty was defined as a clinical frailty scale score of <7. Bleeding and thromboembolic events during the OAC treatment were followed up. RESULTS: Of 354 patients enrolled, 273 (77.1%) received DOACs and 81 (22.9%) received warfarin. Of 273 patients receiving DOACs, there were 210 (76.9%) prescribed with appropriate doses of DOACs. Of 81 warfarin-treated patients, 53 (65.4%) were prescribed an appropriate dose of warfarin. During a follow-up of 33.1 (14.0-51.0) months, 15 patients (1.5/100 person-years) had bleeding events and 10 (1.0/100 person-years) had thromboembolic events while on an OAC treatment. The incidence ratio of bleeding events in patients receiving DOACs was lower than that in those receiving warfarin (1.0/100 person-years vs 2.9/100 person-years, hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.07-0.91, P = .036). There was no significant difference in the incidence of thromboembolic events between the DOAC and warfarin treatment groups (0.88/100 person-years vs 1.4/100 person-years, HR: 0.63, 95% CI: 0.16-2.57, P = .52). CONCLUSIONS: OACs are substantially safe and effective for preventing thromboembolic events in nonsevere frail patients over 80 years of age. Particularly, DOACs can be used more safely than warfarin.

Bleeding with oral anticoagulant dabigatran is highly associated with occult cancers in atrial fibrillation patients.

AIM: The aim of this study was to examine cancer and bleeding in atrial fibrillation patients administered with dabigatran. MATERIALS & METHODS: This study enrolled 509 consecutive nonvalvular atrial fibrillation patients who received dabigatran. The mean administration period was 14.8 ± 15.7 months. We investigated the prevalence and new development of cancers. Further, the relation between cancer and adverse events was evaluated. RESULTS: In the 509 patients, major bleeding occurred in 2.6% and dyspepsia in 8.4%. Further, 16.9% patients had a history of cancer and 3.9% developed new cancers. These adverse events developed in 45% patients who developed new cancers. The cancer (hazard ratio: 6.30; p = 0.003) was a significant predictor of major bleeding. CONCLUSION: Bleeding was associated with the presence of cancer.

Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias.

BACKGROUND: Pilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters. RESULTS: Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments. CONCLUSIONS: DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.