Pacing-induced cardiomyopathy in patients with preserved ejection fraction undergoing permanent cardiac pacemaker placement.

BACKGROUND: Chronic right-ventricular (RV) pacing can worsen heart failure in patients with a low ejection fraction (EF), but little is known about pacing-induced cardiomyopathy (PICM) in patients with preserved EF. We aimed to investigate risk factors of PICM in these patients during long-term follow-up. METHODS: The prospective registry at Chosun University Hospital, South Korea, included de novo patients with preserved EF undergoing transvenous permanent pacemaker (PPM) implantation for atrioventricular blockage from 2017 to 2021. Patients with EF ≥ 50% and expected ventricular pacing ≥ 40% were included. Composite outcomes were cardiac death (pump failure), hospitalization because of heart failure, PICM, and biventricular pacing (BVP) upgrade. RESULTS: A total of 168 patients (69 men, 76.3 ± 10.4 years) were included. During three years of follow-up, one patient died, 14 were hospitalized, 16 suffered PICM, and two underwent BVP upgrade. PICM were associated with reduced global longitudinal strain (GLS), prolonged paced QRS duration (pQRSd) and diastolic variables (E/e', LAVI). Cox regression analysis identified pQRSd (hazard ratio [HR], 1.111; 95% confidence interval [CI], 1.011-1.222; P = 0.03) and reduced GLS (HR, 1.569; 95% CI, 1.163-2.118; P = 0.003) as independent predictors of PICM. GLS showed high predictive accuracy for PICM, with an area under the curve of 0.84 (95% CI 0.779-0.894; P < 0.001) [GLS -12.0, 62.5% sensitivity, and 86.1% specificity]. CONCLUSION: RV pacing increased the risk of PICM in patients with preserved EF. Reduced GLS and prolonged pQRSd could help identify individuals at high risk of PICM even with preserved EF.

Antiarrhythmic Effect of Artemisinin in an Ex-vivo Model of Brugada Syndrome Induced by NS5806.

BACKGROUND AND OBJECTIVES: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (Ito) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of Ito channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. METHODS: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 µM), calcium channel blocker verapamil (1 µM), and Ito agonist NS5806 (6-10 µM) were used. Artemisinin (100-150 µM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. RESULTS: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. CONCLUSIONS: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including Ito channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

Clinical outcomes in patients with atrioventricular block undergoing pacemaker: 3-year follow-up.

PURPOSE: Left ventricular function can be affected by chronic ventricular pacing. Different right ventricular (RV) pacing sites have shown heterogeneous clinical outcomes. We investigated these factors in patients receiving permanent pacemaker (PPM) implants. METHODS: This multicenter, retrospective analysis of PPM use in South Korea, included all patients undergoing de novo transvenous PPM implantation for atrioventricular block from 2017 to 2019. Clinical characteristics, 12-lead electrocardiograms, echocardiography, and laboratory parameters were evaluated. Composite outcomes are defined by two coprimary endpoints: (1) hospitalizations and (2) cardiac death by heart failure during follow-up period. RESULTS: There were 167 patients (66 males; overall mean age 75.3 ± 11.9 years), divided into two groups according to the pacing site: 83 apical RV (RVA) vs. 84 septal RV (RVS). There were no significant baseline differences. Paced QRS duration (pQRSd) increased with RVA (168.5 ± 20.1 vs. 159.1 ± 16.3 ms; p < 0.001). Over a median 31-month follow-up, there were 15 hospitalizations and 2 deaths. More patients with RVA were hospitalized or died (16% vs. 5%, respectively; p = 0.049). In Cox proportional regression analysis, pQRSd (hazard ratio [HR] 1.046; 95% confidence interval [CI] 1.004-1.091; p = 0.033), and diastolic dysfunction (HR 7.343; 95% CI 2.035-26.494; p = 0.002) were independent predictors of composite clinical outcomes. CONCLUSIONS: RVS placement shortened the pQRSd and improved clinical outcomes. However, the determinants of these were pQRSd and diastolic dysfunction. Therefore, clinicians should try to shorten the pQRSd when implanting a PPM, and patients with diastolic dysfunction should be monitored intensively.

A case of sinus arrest in atrial fibrillation with pulmonary embolism after flecainide ingestion.

A 76-year-old female visited the emergency department with complaining of dizziness and syncope. She had a history of paroxysmal atrial fibrillation (AF) and had been prescribed flecainide 50 mg and apixaban 5 mg 12-hourly in another hospital 1 day before the presentation. Upon admission, her electrocardiogram showed profound bradycardia and extremely long sinus arrest, which required temporary cardiac pacing. Within 24 hours, her intrinsic rhythm was restored, and the temporary pacemaker was removed. Transthoracic and transesophageal echocardiography revealed no structural heart disease or thrombus in the left atrial appendage. Cardiac computed tomography showed no coronary artery stenosis, but a pulmonary thrombus in the right pulmonary artery. She underwent an electrophysiology study, and four pulmonary vein (PV) isolations were attempted to treat the paroxysmal AF. A bidirectional PV conduction block was acquired in all PVs despite spontaneous dissociation of PV potential in the right PV. Programmed stimulation following ablation resulted in sinus node dysfunction. After the procedure, the patient did not complain of dizziness and syncope for 72 hours of telemetry monitoring. She was discharged with anticoagulant and did not show any further symptoms for 6 months. Flecainide acetate is a class Ic antiarrhythmics, and its clinical efficacy has been confirmed in several clinical trials. However, it can unmask sinus node dysfunction in asymptomatic patients with paroxysmal AF. Clinicians should screen candidates for sinus nodal diseases when prescribing flecainide.

Post-operative Atrial Fibrillation Impacts on Outcomes in Transcatheter and Surgical Aortic Valve Replacement.

Background: Atrial fibrillation (AF) in severe aortic stenosis (AS) has poor outcomes after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively). We compared the incidence of AF after aortic valve replacement (AVR) according to the treatment method and the impact of AF on outcomes. Methods: We investigated the incidence of AF and clinical outcomes of AVR according to whether AF occurred after TAVR and SAVR after propensity score (PS)-matching for 1 year follow-up. Clinical outcomes were defined as death, stroke, and admission due to heart failure. The composite outcome comprised death, stroke, and admission due to heart failure. Results: A total of 221 patients with severe AS were enrolled consecutively, 100 of whom underwent TAVR and 121 underwent SAVR. The incidence of newly detected AF was significantly higher in the SAVR group before PS-matching (6.0 vs. 40.5%, P < 0.001) and after PS-matching (7.5 vs. 35.6%, P = 0.001). TAVR and SAVR showed no significant differences in outcomes except in terms of stroke. In the TAVR group, AF history did not affect the outcomes; however, in the SAVR group, AF history affected death (log rank P = 0.038). Post-AVR AF had a worse impact on admission due to heart failure (log rank P = 0.049) and composite outcomes in the SAVR group. Post-AVR AF had a worse impact on admission due to heart failure (log rank P = 0.008) and composite outcome in the TAVR group. Conclusion: Post-AVR AF could be considered as a predictor of the outcomes of AVR. TAVR might be a favorable treatment option for patients with severe symptomatic AS who are at high-risk for AF development or who have a history of AF because the occurrence of AF was more frequent in the SAVR group.

Screening for Atrial Fibrillation Using a Single Lead ECG Monitoring Device.

Atrial fibrillation (AF) is the most common arrhythmia which needs management for stroke prevention. Therefore, it has emphasized the importance of screening for general population to detect AF earlier. We conducted screening for AF in the Chonbuk region in South Korea. Participants who were older than 50 years were enrolled. The screening test used a single lead electrocardiography (ECG) (KardiaBand, AliveCor, CA, USA). Diagnosis of AF was confirmed by electrophysiologists, if the single lead ECG demonstrated AF of more than 30 seconds. We analyzed the prevalence of AF and the characteristics of newly detected AF patients. A total of 2728 participants, 145 (5.3%) participants had already been diagnosed with AF before. The number of screening positive was 55. Among them, 40 participants were confirmed for AF. Male gender and age older than 70 years were the independent risk factors for AF among the screening positive participants. Most of newly detected AF patients were at high risk for stroke which had more than 2 points on the CHA2DS2-VASc score. We followed up with those patients and encouraged them to visit the hospital. As a result, 31 (77.5%) patients started to manage AF. The additional 1.2% of AF was detected by a screening test with a single lead ECG monitor device. Considering most participants of newly detected AF by screening were at high risk for stroke, it was thought that AF was still undertreated. Therefore, screening tests with simple mobile device might be useful for early detection of AF.

Implantable cardioverter defibrillator as a treatment for massive left ventricular fibroma-induced ventricular arrhythmia in a child.

Pediatric cardiac tumors are rare. Among these, cardiac fibroma is the second most common. Its clinical manifestations depend on size and location of the tumor and include arrhythmia or obstruction to blood flow. Symptomatic cardiac fibroma is generally treated with surgical resection or cardiac transplantation. We present the case of a 12-year-old boy with a lethal ventricular arrhythmia induced by a remnant tumor that was previously partially resected. An implantable cardioverter defibrillator was inserted as the arrhythmia was resistant to medical treatment. He was discharged in stable condition with an implantable cardioverter defibrillator generator and followed up in the outpatient clinic.

Right Ventricular Longitudinal Conduction Delay in Patients with Brugada Syndrome.

BACKGROUND: The mechanism of Brugada syndrome (BrS) is still unclear, with different researchers favoring either the repolarization or depolarization hypothesis. Prolonged longitudinal activation time has been verified in only a small number of human right ventricles (RVs). The purpose of the present study was to demonstrate RV conduction delays in BrS. METHODS: The RV outflow tract (RVOT)-to-RV apex (RVA) and RVA-to-RVOT conduction times were measured by endocardial stimulation and mapping in 7 patients with BrS and 14 controls. RESULTS: Patients with BrS had a longer PR interval (180 ± 12.6 vs. 142 ± 6.7 ms, P = 0.016). The RVA-to-RVOT conduction time was longer in the patients with BrS than in controls (stimulation at 600 ms, 107 ± 9.9 vs. 73 ± 3.4 ms, P = 0.001; stimulation at 500 ms, 104 ± 12.3 vs. 74 ± 4.2 ms, P = 0.037; stimulation at 400 ms, 107 ±12.2 vs. 73 ± 5.1 ms, P = 0.014). The RVOT-to-RVA conduction time was longer in the patients with BrS than in controls (stimulation at 500 ms, 95 ± 10.3 vs. 62 ± 4.1 ms, P = 0.007; stimulation at 400 ms, 94 ±11.2 vs. 64 ± 4.6 ms, P = 0.027). The difference in longitudinal conduction time was not significant when isoproterenol was administered. CONCLUSION: The patients with BrS showed an RV longitudinal conduction delay obviously. These findings suggest that RV conduction delay might contribute to generate the BrS phenotype.

Defibrillation threshold testing during implantable cardioverter defibrillator implantation: 5-year follow-up.

PURPOSE: Defibrillation threshold (DFT) testing is a routine practice in some Asian countries for patients receiving an implantable cardioverter defibrillator (ICD). However, there are few long-term data about the necessity of intraoperative DFT testing in an Asian population. We investigated the safety of DFT testing and the long-term clinical outcomes in Asian patients undergoing ICD implantation. METHODS: All patients undergoing de novo transvenous ICD implantation were randomized to undergo periprocedural DFT testing. The study included 67 patients (50 males; 51.5 ± 16.9 years) who underwent ICD implantation with (n = 33) or without (n = 34) intraoperative DFT testing between March 2012 and February 2014. We compared first-shock success, composite safety end points (the sum of complications recorded at 30 days), arrhythmic death, and all-cause mortality. RESULTS: The baseline clinical characteristics and the procedural-related adverse event rate (3.0% with DFT vs. 0% with non-DFT, p = 0.214) did not differ between groups. The programmed output of the first shock was lower in the DFT testing group (22.9 ± 4.4 J vs. 25.3 ± 5.4 J, p = 0.007). However, there were no significant differences between groups for all-cause mortality (12.1% vs. 17.6%, p = 0.526) or first-shock success rate for ventricular arrhythmia (100% vs. 88.2%, p = 0.471). CONCLUSIONS: There were no between-group differences in periprocedural safety, complications, and long-term clinical outcomes. Our results suggest that DFT testing in Asian patients allows reduction of the programmed output of the first shock, but does not affect long-term clinical outcomes.

Positive chronotropic effects of theophylline and cilostazol in patients with symptomatic sick sinus syndrome who have declined permanent pacing.

Pacemakers are more commonly recommended than theophylline for sick sinus syndrome (SSS) treatment. The positive effects of cilostazol on bradyarrhythmias also have been reported. However, no comparison of cilostazol and theophylline has been previously reported found. We retrospectively enrolled SSS patients, who refused a pacemaker implantation. Theophylline or cilostazol was administered, and the heart rate (HR) was evaluated in 4-8 weeks using a digital sphygmomanometer and the electrocardiogram (ECG). A 200-400 mg of theophylline or 100-200 mg of cilostazol were administered per day in 50 and 30 patients, respectively. The baseline HR was 54.8 ± 13.5 beats per minute (bpm) on using sphygmomanometry and 51.9 ± 11.8 bpm using the ECG. In the theophylline group, the HR increased by 12.0 ± 16.3 bpm by sphygmomanometry (P < 0.001) and 8.4 ± 12.0 bpm by the ECG (P < 0.001). In the cilostazol group, the HR increased by 16.8 ± 13.9 bpm by sphygmomanometry (P < 0.001) and 12.4 ± 13.4 bpm using the ECG (P < 0.001). In 15 of the 50 theophylline patients, the medication was switched to cilostazol. The HR increased from 61.4 ± 13.8 bpm to 64.0 ± 12.6 bpm (P = 0.338). Symptoms such as dyspnea, chest discomfort, dizziness, and syncope significantly improved after the administration of the medications. There were no significant differences in the improvement in the symptoms except for dizziness between the two agents. Cilostazol was as effective as theophylline for increasing the HR in SSS patients.

Transmural conduction time in an early repolarization syndrome model.

In the pathological aspect of J wave syndrome, delayed depolarization is defined as the difference in local conduction velocity of the ventricular myocardium. If polymorphic ventricular tachycardia is induced without local conduction velocity heterogeneity, this contradicts the delayed depolarization theory. In the present study, the transmural conduction time at was evaluated at several transmural locations in a canine early repolarization model. The transmural pseudo-electrocardiogram and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n=18). The Ito agonist NS5806 (9-10 µM), Ca2+ channel blocker verapamil (2 µM) and acetylcholine (ACh) (2 µM) were used to pharmacologically mimic early repolarization syndrome genotypes. The transmural conduction times were measured at five fixed epicardial unipolar electrodes before and after the perfusion of provocative agents. The transmural conduction time was defined as the time from endocardial stimulation to the maximal negative deflection (dV/dt) of the endocardial electrogram at the unipolar electrode. Polymorphic ventricular tachycardia developed in 14/18 preparations. In the transmembrane action potentials, there was no definite delayed phase 0 upstroke in any induced polymorphic ventricular tachycardia preparations. In all preparations, the transmural conduction time increased significantly after perfusing the Ito agonist NS5806, verapamil and Ach; however, the increase was only 2.6±0.4 msec, and dispersion of the transmural conduction time did not exhibit significant heterogeneity (7.16±0.93 vs. 7.76±1.21 msec; P=0.240). In the early repolarization model, polymorphic ventricular tachycardia was induced without any regional conduction velocity heterogeneity. This finding suggests that local depolarization heterogeneity would not be a major contributor to the generation of ventricular arrhythmia in the early repolarization syndrome wedge preparation model.

Radiofrequency catheter ablation without radiation exposure in a 13th week pregnant woman with Wolff-Parkinson-White syndrome.

A 36-year-old woman with 12-week gestation visited the emergency department, complaining of palpitations. Her electrocardiography (ECG) demonstrated ventricular pre-excitation combined with atrial fibrillation. The polarity of the delta waves in leads V5, V6, I, and aVL were positive and negative in leads V1, III, and aVF, suggesting that the accessory pathway (AP) was located on the right posterior free wall. She did not want to take any medicine to prevent the tachycardia. Moreover, the shortest pre-excited RR interval during the atrial fibrillation was 200 ms, so we decided to ablate the AP without fluoroscopy. An electrophysiology study was performed with guidance of a 3-dimension (3D) navigation system and intracardiac echocardiography (ICE). We ablated the right free wall AP without fluoroscopy. A follow-up ECG no longer exhibited any delta waves. Even in the early period of pregnancy, catheter ablation might be performed safely using ICE and a 3D navigation system without fluoroscopy. Therefore, it could more often be considered as a therapeutic option in pregnant women without concern for radiation exposure.

Impact of Anticoagulation Intensity in Korean Patients with Atrial Fibrillation: Is It Different from Western Population?

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients. METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death. RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6-2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19-0.85), major bleeding (HR, 0.43; 95% CI, 0.23-0.81), primary (HR, 0.50; 95% CI, 0.29-0.84) and secondary (HR, 0.45; 95% CI, 0.28-0.74) net-clinical outcomes, whereas mean INR 2.0-3.0 did not. Simultaneous satisfaction of mean INR 1.6-2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes. CONCLUSIONS: Mean INR 1.6-2.6 was better than mean INR 2.0-3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6-2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0-3.0 and TTR ≥70% in Korean patients with non-valvular AF.