Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Edoxaban-based long-term antithrombotic therapy in patients with atrial fibrillation and stable coronary disease: Rationale and design of the randomized EPIC-CAD trial.

BACKGROUND: Anticoagulants are the standard therapy for patients with atrial fibrillation (AF) and antiplatelet therapy for those with coronary artery disease (CAD). However, compelling clinical evidence is still lacking regarding the long-term maintenance strategy with the combination of anticoagulant and antiplatelet drugs in patients with AF and stable CAD. DESIGN: The EPIC-CAD trial is an investigator-initiated, multicenter, open-label randomized trial comparing the safety and efficacy of 2 antithrombotic strategies in patients with high-risk AF (CHA2DS2-VASc score ≥ 2 points) and stable CAD (≥6 months after revascularization for stable angina or ≥12 months for acute coronary syndrome; or medical therapy alone). Patients (approximately N = 1,038) will be randomly assigned at a 1:1 ratio to (1) monotherapy with edoxaban (a non-vitamin K antagonist oral anticoagulant) or (2) combination therapy with edoxaban plus a single antiplatelet agent. The primary endpoint is the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant nonmajor bleeding at 1 year after randomization. RESULTS: As of December 2021, approximately 901 patients had been randomly enrolled over 2 years at 18 major cardiac centers across South Korea. The completed enrollment is expected at the mid-term of 2022, and the primary results will be available by 2023. CONCLUSIONS: EPIC-CAD is a large-scale, multicenter, pragmatic design trial, which will provide valuable clinical insight into edoxaban-based long-term antithrombotic therapy in patients with high-risk AF and stable CAD.

The advantage of the mini-electrode-equipped catheter for the radiofrequency ablation of paroxysmal supraventricular tachycardia.

INTRODUCTION: Novel ablation catheters equipped with mini-electrodes (ME) offer high resolution mapping for target tissue. This study aimed to evaluate the mapping performance and efficacy of ME catheters in radiofrequency ablation (RFA) of paroxysmal supraventricular tachycardias (PSVTs). METHODS: We prospectively enrolled 136 patients undergoing RFA of PSVT including 76 patients with atrioventricular nodal reentrant tachycardia (AVNRT) and 60 patients with atrioventricular reentrant tachycardia (AVRT) or Wolff-Parkinson-White (WPW) syndrome. Patients were randomized to the ME group (ablation using ME catheters) or the control group (ablation using conventional catheters). The number of ablation attempt and cumulative ablation time to ablation endpoints, which was defined as an emergence of junctional rhythm in AVNRT or accessory pathway (AP) block in AVRT/WPW syndromes were compared. RESULTS: During ablation procedures, discrete slow pathway or AP electrograms were found in 27 (39.7%) patients in the ME group and 13 (19.1%) patients in the control group. The primary study outcomes were significantly lower in the ME group (ablation attempt number: 2.0 [1-4] vs. 3.0 [2-7] in the ME and control group, p = .032; ablation time: 23.5 [5.0-111.5] vs. 64.5 [16.0-185.0] s, p = .013). According to the PSVT diagnosis, ablation time to junctional rhythm was significantly shorter in the ME group in AVNRT. In AVRT/WPW syndrome, both ablation attempt number and ablation time to AP block were nonsignificantly lower in the ME group. CONCLUSION: The novel ME catheter was advantageous for identifying pathway potentials and reducing initial ablation attempt number and ablation time to reach acute ablation endpoint for PSVTs (ClinicalTrials.gov number, NCT04215640).

Outcomes of On-Label Reduced-Dose Edoxaban in Patients With Atrial Fibrillation: The LEDIOS Registry.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are effective in preventing thromboembolisms and reduce the risk of bleeding compared with warfarin. There are few reports on the outcomes of on-label reduced-dose NOACs. The aim of this study was to assess the safety and efficacy of on-label reduced-dose edoxaban in patients with atrial fibrillation (AF). METHODS: This study is a multi-center, prospective, non-interventional study to evaluate the safety and efficacy of on-label reduced-dose edoxaban in patients with AF. We evaluated outcomes of major bleeding, stroke or systemic embolism, all-cause death, and composite clinical outcomes. RESULTS: A total of 2,448 patients (mean age 75.0 ± 8.3 years, 801 [32.7%] males) was included in the present study. The mean CHA2DS2-VASc score was 3.7 ± 1.5. Major bleeding events occurred at a rate of 1.34%/yr. The event rate of strokes and systemic embolisms was 1.13%/yr. The overall net clinical outcomes occurred at a rate of 3.19%/yr. There were no significant differences according to the number of dose reduction criteria, renal dysfunction, or body weight. Higher HAS-BLED score and higher combination of CHA2DS2-VASc and HAS-BLED score was associated with an increased risk of composite clinical outcomes compared to the lower score groups. CONCLUSIONS: This study was the largest prospective real-world study to investigate the safety and efficacy of on-label low-dose edoxaban in an Asian population. Reduced-dose edoxaban can be used safely in patients with severe renal dysfunction or extremely low body weight. Our observation suggests that physicians should consider bleeding risk even in a low-dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03554837.

Usefulness of an Implantable Loop Recorder in Diagnosing Unexplained Syncope and Predictors for Pacemaker Implantation.

BACKGROUND: An implantable loop recorder (ILR) is an effective tool for diagnosing unexplained syncope (US). We examined the diagnostic utility of an ILR in detecting arrhythmic causes of US and determining which clinical factors are associated with pacemaker (PM) implantation. METHODS: This retrospective, multicenter, observational study was conducted from February 2006 to April 2018 at 11 hospitals in Korea. Eligible patients with recurrent US received an ILR to diagnose recurrent syncope and document arrhythmia. RESULTS: A total of 173 US patients (mean age, 67.6 ± 16.5 years; 107 men [61.8%]) who received an ILR after a negative conventional workup were enrolled. During a mean follow-up of 9.4 ± 11.1 months, 52 patients (30.1%) had recurrent syncope, and syncope-correlated arrhythmia was confirmed in 34 patients (19.7%). The ILR analysis showed sinus node dysfunction in 24 patients (70.6%), supraventricular tachyarrhythmia in 4 (11.8%), ventricular arrhythmia in 4 (11.8%), and sudden atrioventricular block in 2 (5.9%). Overall, ILR detected significant arrhythmia in 99 patients (57.2%) irrespective of syncope. Among patients with clinically relevant arrhythmia detected by ILR, PM implantation was performed in 60 (34.7%), an intra-cardiac defibrillator in 5 (2.9%), and catheter ablation in 4 (2.3%). In a Cox regression analysis, history of paroxysmal atrial fibrillation (PAF) (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.33-4.12; P < 0.01) and any bundle branch block (BBB) (HR, 2.52; 95% CI, 1.09-5.85; P = 0.03) were significantly associated with PM implantation. CONCLUSION: ILR is useful for detecting syncope-correlated arrhythmia in patients with US. The risk of PM is high in US patients with a history of PAF and any BBB.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Variants of Brugada Syndrome and Early Repolarization Syndrome: An Expanded Concept of J-Wave Syndrome.

BACKGROUND: The role of J-waves in the pathogenesis of ventricular fibrillation (VF) occurring in structurally normal hearts is important. METHODS: We evaluated 127 patients who received an implantable cardioverter-defibrillator (ICD) for Brugada syndrome (BS, n = 53), early repolarization syndrome (ERS, n = 24), and patients with unknown or deferred diagnosis (n = 50). Electrocardiography (ECG), clinical characteristics, and ICD data were analyzed. RESULTS: J-waves were found in 27/50 patients with VF of unknown/deferred diagnosis. The J-waves were reminiscent of those seen in BS or ERS, and this subgroup of patients was termed variants of ERS and BS (VEB). In 12 VEB patients, the J/ST/T-wave morphology was coved, although amplitudes were <0.2 mV. In 15 patients, noncoved-type J/ST/T-waves were present in the right precordial leads. In the remaining 23 patients, no J-waves were identified. VEB patients exhibited clinical characteristics similar to those of BS and ERS patients. Phenotypic transition and overlap were observed among patients with BS, ERS, and VEB. Twelve patients with BS had background inferolateral ER, while five ERS patients showed prominent right precordial J-waves. Patients with this transient phenotype overlap showed a significantly lower shock-free survival than the rest of the study patients. CONCLUSIONS: VEB patients demonstrate ECG phenotype similar to but distinct from those of BS and ERS. The spectral nature of J-wave morphology/distribution and phenotypic transition/overlap suggest a common pathophysiologic background in patients with VEB, BS, and ERS. Prognostic implication of these ECG variations requires further investigation.

Complications of Cardiac Perforation and Lead Dislodgement with an MRI-Conditional Pacing Lead: a Korean Multi-Center Experience.

Medtronic CapSureFix MRI 5086 pacing lead (5086; Medtronic, Inc., Minneapolis, MN, USA) has been reported to be associated with increased cardiac perforation and lead dislodgement. This study aimed to compare the incidence of cardiac perforation and lead dislodgement within 30 days after pacemaker implantation between 5086 MRI lead and previous Medtronic CapSureFix Novus 5076 non-MRI pacing lead. This was a nationwide, multicenter retrospective study in which we compared the incidence of adverse events between 277 patients implanted with 5086 lead and 205 patients implanted with 5076 lead between March 2009 and September 2014. Cardiac perforation within 30 days of pacemaker implantation occurred in 4 patients (1.4%) with the 5086 lead and in no patient with the 5076 lead (P = 0.084). Lead dislodgement occurred in 8 patients (2.9%) with the 5086 lead and in 5 patients (2.4%) with the 5076 lead (P = 0.764). On multivariate logistic regression analysis, age was significantly associated with cardiac perforation. Congestive heart failure and implantation of right atrial (RA) lead at RA free wall or septum were significant factors for the incidence of lead dislodgement and lead revision. The incidence of cardiac perforation and lead dislodgement were not statistically different between the patients with 5086 lead and the patients with 5076 lead. However, careful attention for cardiac perforation may be needed when using the 5086 MRI lead, especially in elderly patients.

Restoration of Mitral Inflow Velocity Until Blanking Period Is Associated With Successful Ablation for Persistent Atrial Fibrillation.

Radiofrequency catheter ablation (RFCA) is a useful therapeutic option for atrial fibrillation (AF), although outcomes are less effective for persistent AF. The aim of this study was to elucidate the echocardiographic parameters associated with successful RFCA in patients with persistent AF.A total of 159 patients (mean age, 60.8 ± 9.6 years, 125 males [78.6%]) who underwent RFCA for persistent AF from April 2009 to May 2014 were included, retrospectively. Transthoracic echocardiography was performed at baseline, 3 months, 6 months, and 1 year following RFCA. The subjects were divided into 2 groups, a recurrence group and a non-recurrence group. One hundred eleven of the 159 patients (69.8%) remained free from recurrent atrial tachyarrhythmia during follow-up (mean, 20.6 ± 17.4 months). Peak A wave velocity (38.1 ± 14.1 in the recurrence group; 48.0 ± 20.7 in the non-recurrence group, P = 0.01), peak E wave velocity (76.4 ± 19.1 versus 68.8 ± 19.5, P = 0.03), deceleration time (196.3 ± 54.4 versus 219.9 ± 64.1, P = 0.04), and left atrial (LA) diameter (44.5 ± 7.3 versus 41.0 ± 5.6, P = 0.01) at 3 months after ablation were significantly different between the two groups. Among echocardiographic parameters, peak A wave velocity (OR 0.96, 95% confidence interval [CI] 0.92-0.99) and LA diameter (OR 1.13, 95% CI 1.011.25) were associated with AF recurrence.After RFCA for persistent AF, LA anatomical and functional changes occurred during a 3-month blanking period. Restoration of peak A wave velocity and LA size are associated with successful ablation.

Impact of left anterior line on left atrial appendage contractility in patients who underwent catheter ablation for chronic atrial fibrillation.

BACKGROUND: Left anterior line (LAL) has been used as a substitute for mitral isthmus line for catheter ablation of chronic atrial fibrillation (AF). However, it results in left anterolateral conduction delay and might affect left atrial (LA) contractility. We aimed to investigate whether LAL decreases LA appendage function. METHODS: This study included 46 patients (30 men, mean age 58 ± 9 years, group 1) with persistent AF who underwent catheter ablation including LAL. Thirty patients with paroxysmal AF who received no additional LA ablation were compared as control group (21 males, mean age 56 ± 8 years, group 2). Transthoracic and transesophageal echocardiography with Doppler tissue imaging was performed in sinus rhythm before and after the ablation. We compared the following variables: (1) E/A ratio of the mitral flow velocity, (2) ratio of early mitral inflow and mitral septal annulus velocity (E/Em), (3) peak velocity of appendage outflow (ApVmax), and (4) time delay from QRS onset to appendage outflow (TDqa). RESULTS: LA diameter was significantly reduced after ablation in both groups. In group 1, parameters for diastolic function (E/A ratio, 1.7 ± 0.5 vs 2.0 ± 0.6, P = 0.197; E/Em, 11.7 ± 4.8 vs 11.6 ± 5.1, P = 0.883) and appendage flow (ApVmax, 55.2 ± 19.9 cm/s vs 50.3 ± 19.3 cm/s, P = 0.203; TDqa, -77.3 ± 30.1 ms vs -66.1 ± 60.8 ms, P = 0.265) did not change significantly after ablation. Changes of ApVmax and TDqa after ablation were not significantly different between two groups (P = 0.409 and P = 0.195, respectively). CONCLUSIONS: LAL ablation did not aggravate mitral flow pattern or change appendage outflow. LAL could be used without concern over worsening LA diastolic and appendage function.

Upper common pathway analysis using late atrial premature depolarization in atrioventricular nodal reentry tachycardia.

BACKGROUND: Anatomic and electrophysiologic findings suggest that the actual circuit of atrioventricular nodal reentrant tachycardia (AVNRT) involves the perinodal atrium. However, occasional instances in which the atrium is dissociated from the AVNRT have led to the concept of an upper common pathway (UCP). OBJECTIVE: We aimed to assess the prevalence of UCP in AVNRT using a late atrial premature depolarization (LAPD) maneuver. METHODS: Patients who were diagnosed with typical AVNRT by electrophysiologic studies were enrolled. For evaluation of the presence of UCP, an LAPD was given at the coronary sinus ostium (osCS) during AVNRT, and then pacing was repeated incrementally every 10 ms. Electrograms in the earliest retrograde atrial activation site (ERAS) near the proximal His were mapped and recorded during the pacing. Results were interpreted as follows: absence of UCP-an LAPD from the osCS can reset the tachycardia without depolarizing the ERAS; presence of UCP-an LAPD from the osCS can depolarize the ERAS without resetting the tachycardia; and indeterminate-an LAPD from the osCS either resets the ERAS and tachycardia simultaneously or does not reset both. RESULTS: The LAPD maneuver was performed in 126 patients with AVNRT. It demonstrated an absence of UCP in 121 (96.0%) patients and the presence of UCP in 3 (2.4%) patients; the result was indeterminate in 2 (1.6%) patients. CONCLUSION: The LAPD maneuver revealed that the presence of UCP is indicated in only rare cases of AVNRT. In most AVNRT cases, the atrium is involved in the reentry circuit.

Clinical outcomes with the use of sodium-glucose cotransporter-2 inhibitors in patients with atrial fibrillation and type 2 diabetes mellitus: a multi-centre, real-world cohort study.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular outcomes and reduce the incidence of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We investigated the clinical outcomes with and without the use of SGLT2is in patients with T2DM and concomitant AF. METHODS AND RESULTS: We derived patient data from a clinical data warehouse constructed from the electronic medical records of seven medical centres. Data for 11 012 patients diagnosed with both AF and T2DM were analysed. New SGLT2i users were classified into the SGLT2i group and those who were not prescribed SGLT2is were classified into the control group. We performed a 1:2 propensity score (PS)-matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure (HF) events in 3 years. The PS-matched population consisted of 1115 patients in the SGLT2i group and 2050 patients in the control group. Incidence of the primary endpoint was significantly lower in the SGLT2i group [8.4 vs. 14.6%, hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.55-0.87]. Sodium-glucose cotransporter-2 inhibitors use was associated with significantly lower all-cause mortality (HR 0.43, 95% CI 0.29-0.67) and HF hospitalization (HR 0.77, 95% CI 0.59-0.99). Adverse renal events, defined as >50% increase in serum creatinine level or initiation of dialysis, occurred less often in the SGLT2i group (HR 0.50, 95% CI 0.38-0.66, P < 0.001). CONCLUSION: Use of SGLT2is in patients with T2DM and concomitant AF was associated with reduced mortality or HF hospitalization events.

In this multi-centre, registry-based analysis, the new use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with atrial fibrillation and type 2 diabetes mellitus was associated with lower all-cause mortality or hospitalization due to heart failure (HF) events. All-cause mortality, HF hospitalization, ischaemic stroke, and composite renal outcomes, defined as >50% decline in renal function or new initiation of dialysis occurred significantly less in the SGLT2i new users, compared with the propensity score-matched controls. The difference in outcomes between the SGLT2i group and control group was more pronounced in patients with higher HbA1c at baseline and prior HF.

Clinical impact of capsulectomy during cardiac implantable electronic device generator replacement: a prospective randomized trial.

BACKGROUND: The avascular capsule around the generator of the cardiac implantable electronic device (CIED) could be susceptible to bacterial colonization and source of infection. Capsulectomy during CIED generator replacement may be beneficial in preventing device infection, but there is a lack of evidence. METHODS: This prospective randomized trial, conducted from December 2013 to December 2019, included 195 patients divided equally into two groups. In the intervention group (n = 97), capsule removal was performed on the floor of the pocket, while it was not performed in the control group (n = 98). In both groups, swab culture was performed in the pocket. The primary outcome was the occurrence of device infection requiring pocket revision. RESULTS: A total of 195 patients were included (mean age 70.2 ± 13.6 years, 55.4% women), with an average follow-up period of 54.3 ± 28.9 months. Among 182 patients undergoing microbiological cultures of pockets, 19 (10.4%) were confirmed positive, and Staphylococcus species were identified most frequently. The primary outcome occurred in 4 (2.1%), and there was no significant difference between the two groups (3.1% vs. 1.0%, p = 0.606). Hematoma has occurred in 10 patients (3.1% vs. 7.1%, p = 0.338), one of them required wound revision. In multivariable analysis, the occurrence of hematoma was the only independent risk factor associated with device infection (HR 13.6, 95% CI 1.02-181.15, p = 0.048). CONCLUSIONS: In this long-term prospective study, capsulectomy during the replacement of the generator did not reduce the incidence of device infection. There was no association between bacterial colonization in the capsule around the generator and CIED infection.

Single nucleotide deletion mutation of KCNH2 gene is responsible for LQT syndrome in a 3-generation Korean family.

Long QT syndrome (LQTS) is characterized by the prolongation of the QT interval in ECG and manifests predisposition to life threatening arrhythmia which often leads to sudden cardiac death. We encountered a 3-generation family with 5 affected family members in which LQTS was inherited in autosomal dominant manner. The LQTS is considered an ion channel disorder in which the type and location of the genetic mutation determines to a large extent the expression of the clinical syndrome. Upon screening of the genomic sequences of cardiac potassium ion channel genes, we found a single nucleotide C deletion mutation in the exon 3 of KCNH2 gene that co-segregates with the LQTS in this family. This mutation presumably resulted in a frameshift mutation, P151fs+15X. This study added a new genetic cause to the pool of mutations that lead to defected potassium ion channels in the heart.

Effectiveness of Early Direct Oral Anticoagulant Monotherapy within One Year of Coronary Stent Implantation in Patients with Atrial Fibrillation: A Nationwide Population-Based Study.

We evaluated the effectiveness of early direct oral anticoagulant (DOAC) monotherapy within one year after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) using Korean National Health Insurance Service data. AF patients who underwent PCI were included and divided into the DOAC monotherapy group and the combination therapy group (DOAC with an antiplatelet agent) based on the medications used at 6 months after PCI. A major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, acute myocardial infarction (AMI), stroke, or systemic thromboembolic event between 6 and 12 months after PCI. In the overall study population, the DOAC dose reduction rate was high in both the monotherapy group (70.8%) and the combination therapy group (79.1%). After propensity score matching, the MACE incidence was not significantly different between the two groups (hazard ratio [HR] 1.42 [0.90-2.24]). The numerical trend for higher MACE in the monotherapy group was mainly driven by the difference in stroke incidence (HR 1.84 [0.97-3.46]). All-cause death (HR 1.29 [0.61-2.74] or the incidence of major bleeding (HR 1.07 [0.49-2.35]) results were similar in the two groups. In conclusion, early DOAC monotherapy was not significantly associated with MACE risk between 6 and 12 months after PCI.