Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.

BACKGROUND: The pathogenic missense variant p.G125R in TBX5 (T-box transcription factor 5) causes Holt-Oram syndrome (also known as hand-heart syndrome) and early onset of atrial fibrillation. Revealing how an altered key developmental transcription factor modulates cardiac physiology in vivo will provide unique insights into the mechanisms underlying atrial fibrillation in these patients. METHODS: We analyzed ECGs of an extended family pedigree of Holt-Oram syndrome patients. Next, we introduced the TBX5-p.G125R variant in the mouse genome (Tbx5G125R) and performed electrophysiologic analyses (ECG, optical mapping, patch clamp, intracellular calcium measurements), transcriptomics (single-nuclei and tissue RNA sequencing), and epigenetic profiling (assay for transposase-accessible chromatin using sequencing, H3K27ac [histone H3 lysine 27 acetylation] CUT&RUN [cleavage under targets and release under nuclease sequencing]). RESULTS: We discovered high incidence of atrial extra systoles and atrioventricular conduction disturbances in Holt-Oram syndrome patients. Tbx5G125R/+ mice were morphologically unaffected and displayed variable RR intervals, atrial extra systoles, and susceptibility to atrial fibrillation, reminiscent of TBX5-p.G125R patients. Atrial conduction velocity was not affected but systolic and diastolic intracellular calcium concentrations were decreased and action potentials were prolonged in isolated cardiomyocytes of Tbx5G125R/+ mice compared with controls. Transcriptional profiling of atria revealed the most profound transcriptional changes in cardiomyocytes versus other cell types, and identified over a thousand coding and noncoding transcripts that were differentially expressed. Epigenetic profiling uncovered thousands of TBX5-p.G125R-sensitive, putative regulatory elements (including enhancers) that gained accessibility in atrial cardiomyocytes. The majority of sites with increased accessibility were occupied by Tbx5. The small group of sites with reduced accessibility was enriched for DNA-binding motifs of members of the SP (specificity protein) and KLF (Krüppel-like factor) families of transcription factors. These data show that Tbx5-p.G125R induces changes in regulatory element activity, alters transcriptional regulation, and changes cardiomyocyte behavior, possibly caused by altered DNA binding and cooperativity properties. CONCLUSIONS: Our data reveal that a disease-causing missense variant in TBX5 induces profound changes in the atrial transcriptional regulatory network and epigenetic state in vivo, leading to arrhythmia reminiscent of those seen in human TBX5-p.G125R variant carriers.

Effects of radiofrequency catheter ablation for premature ventricular complexes originating from the right ventricular outflow tract on right ventricular function.

INTRODUCTION: This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. METHODS: A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. RESULTS: PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p < .001). FAC and GLS were significantly worse in proportion to PVC burden (p < .001 and p < .001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052-1.134); p < .001]. Improvement in FAC (13.0 ± 8.7% and -2.5 ± 5.6%, respectively; p < .001) and GLS (-6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p < .001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. CONCLUSIONS: Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA.

A Variant Noncoding Region Regulates Prrx1 and Predisposes to Atrial Arrhythmias.

[Figure: see text].

Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome.

AIMS: Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings. METHODS AND RESULTS: Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0-67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1-2 years (n = 339), 2-5 years (n = 308), and after 5 years (CR>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P < 0.001), and use of post-procedure anti-arrhythmic drugs (P < 0.001) were lower. A CR>5 yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98-1.00), P = 0.035], low LA voltage [OR 0.61 (0.38-0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23-0.67), P < 0.001]. Extra-pulmonary vein triggers during repeat procedures were significantly greater in patients with a CR>5 yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330). CONCLUSIONS: Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.

Changes in the Circadian Rhythm of High-Frequency Heart Rate Variability Associated With Depression.

BACKGROUND: Heart rate variability (HRV) extracted from electrocardiogram measured for a short period during a resting state is clinically used as a bio-signal reflecting the emotional state. However, as interest in wearable devices increases, greater attention is being paid to HRV extracted from long-term electrocardiogram, which may contain additional clinical information. The purpose of this study was to examine the characteristics of HRV parameters extracted through long-term electrocardiogram and explore the differences between participants with and without depression and anxiety symptoms. METHODS: Long-term electrocardiogram was acquired from 354 adults with no psychiatric history who underwent Holter monitoring. Evening and nighttime HRV and the ratio of nighttime-to-evening HRV were compared between 127 participants with depressive symptoms and 227 participants without depressive symptoms. Comparisons were also made between participants with and without anxiety symptoms. RESULTS: Absolute values of HRV parameters did not differ between groups based on the presence of depressive or anxiety symptoms. Overall, HRV parameters increased at nighttime compared to evening. Participants with depressive symptoms showed a significantly higher nighttime-to-evening ratio of high-frequency HRV than participants without depressive symptoms. The nighttime-to-evening ratio of HRV parameters did not show a significant difference depending on the presence of anxiety symptoms. CONCLUSION: HRV extracted through long-term electrocardiogram showed circadian rhythm. Depression may be associated with changes in the circadian rhythm of parasympathetic tone.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation.

BACKGROUND: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF. METHODS: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately. RESULTS: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHA2DS2-VASc score of at least 3. CONCLUSIONS: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.

Increased risk of ischemic stroke and systemic embolism in hyperthyroidism-related atrial fibrillation: A nationwide cohort study.

BACKGROUND: We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF. METHODS: This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related ("nonthyroidal") atrial fibrillation patients. RESULTS: After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P < 0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24 - 1.50; P < 0.001). This difference was also observed in the CHA2DS2-VASc score subgroup analysis. The risk of ischemic stroke and systemic embolism significantly decreased in patients treated for hyperthyroidism (HR, 0.64; 95% CI, 0.58 to 0.70; P < 0.001). CONCLUSIONS: Hyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism.

Ethnic similarities in genetic polymorphisms associated with atrial fibrillation: Far East Asian vs European populations.

BACKGROUND: In European ancestry, 111 genetic loci were identified as associated with atrial fibrillation (AF). We explored the reproducibility of those single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) meta-analysis of Far East Asian populations. METHODS: We performed a meta-analysis of the Korean AF network and Japanese AF data sets (9118 cases and 33 467 controls) by an inverse-variance fixed-effects model. We compared the results with 111 previously reported SNPs proven in Europeans after excluding 36 missing loci and a locus with a minor allelic frequency (MAF) < 0.01 in the European population. RESULTS: Among remaining 74 loci, 29 loci were replicated at a P < .05, and 17 of those loci were newly found in the Far East Asian population: 3 loci with a P < 5×10-8 (METTL11B at 1q24, KCNN2 at 5q22 and LRMDA at 10q22), 4 loci at the threshold of the Bonferroni correction of P = 4.5 × 10-4  ~ 5×10-8 (KIF3C at 2p23, REEP3, NRBF2 at 10q21, SIRT1, MYPN at 10q21 and CFL2 at 14q13) and 10 SNPs with a P = .05 ~ 4.5 × 10-4 . Among 18 AF loci with a MAF< 0.01 in the Far East Asian populations, 2 loci (GATA4 at 8q23 and SGCG at 13q12) were replicated after a fine mapping. Twenty-seven AF loci, including a locus, which had a sufficient sample size to get a power of over 80% (with a type 1 error α = 4.5 × 10-4 ), were not replicated in the Far East Asian populations. CONCLUSIONS: We newly replicated 19 AF-associated genetic loci in the European descent among the Far East Asian populations. It highlights the extensive sharing of AF genetic risks across Far East Asian populations.

Atrial fibrillation and the risk of ischaemic strokes or intracranial haemorrhages: comparisons of the catheter ablation, medical therapy, and non-atrial fibrillation population.

AIMS: Although atrial fibrillation (AF) catheter ablation (AFCA) is an effective rhythm control strategy, there is limited data on whether ischaemic stroke (IS) or intracranial haemorrhage (ICH) decreases after AFCA compared with medical therapy or non-AF population. We explored the IS and ICH risk after AFCA or medical therapy in the AF population and matched non-AF population. METHODS AND RESULTS: We compared 1629 patients with AFCA (Yonsei AF ablation cohort), 3258 with medical therapy [Korean National Health Insurance (NHIS) database], and 3258 non-AF subjects (NHIS database) following a 1:2:2 propensity score matching. All AFCA patients underwent regular rhythm follow-ups for 51 ± 29 months. Among the AFCA group, the incidence rate ratio (IRR) of ISs was significantly higher in patients with sustained AF recurrences after the last ablation (0.87%) than in those remaining in sinus rhythm (0.24%, P = 0.017; log rank P = 0.003). The IRR of ISs was significantly higher in the medical therapy (1.09%) than AFCA (0.30%, P < 0.001, log rank P < 0.001 vs. medical therapy) or non-AF groups (0.34%, P < 0.001, log rank P < 0.001 vs. medical therapy; P = 0.673, log rank P = 0.874 vs. AFCA). The IRR of ICHs was 0.17% in the medical therapy, 0.06% in the AFCA (P = 0.023, log rank P = 0.042 vs. medical therapy), and 0.12% in the non-AF group (P = 0.226, log rank P = 0.241 vs. medical therapy; P = 0.172, log rank P = 0.193 vs. AFCA). CONCLUSION: Post-procedural AF control influences the risk of ISs. Atrial fibrillation catheter ablation significantly reduces the risk of both ISs and ICHs to the extent of the non-AF population compared to the medical therapy.

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

AIMS: The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. METHODS AND RESULTS: A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom ß-blocker were not prescribed. CONCLUSION: Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

AIMS: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). METHODS AND RESULTS: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. CONCLUSION: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

Frailty and the Effect of Catheter Ablation in the Elderly Population With Atrial Fibrillation　- A Real-World Analysis.

BACKGROUND: It is unclear whether catheter ablation is beneficial for frail elderly patients with atrial fibrillation (AF). This study evaluated the effect of ablation on outcomes in frail elderly patients with AF.Methods and Results:From the Korean National Health Insurance Service database, 194,928 newly diagnosed AF patients were treated with ablation or medical therapy (rhythm or rate control) between 2005 and 2015. Among these patients, the study included 1,818 (ablation; n=119) frail and 1,907 (ablation; n=230) non-frail elderly (≥75 years) patients. Propensity score matching was used to correct for differences between groups. During 28 months (median) follow up, the risk of all-cause death, composite outcome (all-cause death, heart failure admission, stroke/systemic embolism, and sudden cardiac arrest), and each outcome did not change after ablation in frail elderly patients. However, in non-frail elderly patients, ablation was associated with a lower risk of all-cause death (3.5 and 6.2 per 100 person-years; hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.30-0.79; P=0.004), and composite outcome (6.9 and 11.2 per 100 person-years; HR 0.54; 95% CI 0.38-0.75; P<0.001). CONCLUSIONS: Ablation may be associated with a lower risk of death and composite outcome in non-frail elderly, but the beneficial effect of ablation was not significant in frail elderly patients with AF. The effect of frailty on the outcome of ablation should be evaluated in further studies.

Clinical Outcomes of Implantable Cardioverter-Defibrillator in Pediatric Patients　- A Korean Multicenter Study.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is important for the prevention of sudden cardiac death, but data on clinical outcomes of ICD therapy in Asian pediatric patients are scarce. The aim of this Korean multicenter study was to evaluate the current state and elucidate the clinical outcomes of ICD therapy in children.Methods and Results:Data from 5 pediatric cardiology centers were retrospectively collected from 2007 to 2019. Altogether, 99 patients were enrolled (mean age 13.9±4.1 years). The most common underlying disease was a primary electrical disease (56%). An ICD was implanted for primary prevention in 19%. Appropriate shock occurred in 44% of patients at a median of 1.6 years after implantation. There was no significant difference in the appropriate shock rate between patients with primary and secondary prevention indications (32% vs. 48%, respectively). A total of 33 patients (33%) experienced inappropriate shock, which was associated with primary electrical disease and follow-up duration on multivariate analysis. 17% of patients had ICD-related complications. CONCLUSIONS: The utilization rate of ICD for primary prevention was still low in the pediatric population in Korea, but there was a substantial rate of appropriate shock in these patients. Efforts to increase ICD usage to save the lives of high-risk patients and reduce the incidence of inappropriate shock are required.

Long-term prognosis of short QT interval in Korean patients: a multicenter retrospective cohort study.

BACKGROUND: Short QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but the characteristics and prognosis of short QT interval (SQTI) in Korean patients remain unclear. This study aimed to determine the clinical characteristics and outcomes of SQTI in a Korean population. METHODS: Consecutive patients with SQTI from January 1999 to March 2019 in three university hospitals in South Korea were recruited. SQTI was defined as a Bazett's formula-corrected QT interval (QTc) ≤ 340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included in a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI. RESULTS: 34 patients with SQTI [age, 23.5 (21-30.5) years; 31 male] were followed up for 4.8 (2.0-7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than in those without SQTI. QT dispersion [44.0 (28.0-73.0) vs. 20.0 (12.0-35.0) ms, P < 0.001] was significantly wider and heart rate [52.0 (47.0-58.0) vs. 70.0 (62.3-84.0)/min, P < 0.001] was significantly slower in patients with SQTI than in those without. Atrial fibrillation (AF, 11.8% vs. 2.2%, P = 0.030) and ventricular arrhythmia (VA)/SCA (8.7% vs. 0%, P = 0.007) were significantly more frequent in patients with SQTI than in those without. SQTI was significantly associated with AF [odds ratio, 5.911; 95% confidence interval, 1.257-27.808; P = 0.025] and VA/SCA. CONCLUSIONS: In this subset of Korean population, SQTI was associated with AF and VA/SCA.

Subclinical cardiac perforation by cardiac implantable electronic device leads detected by cardiac computed tomography.

BACKGROUND: The relationship between the characteristics of cardiac implantable electronic device (CIED) leads and subclinical cardiac perforations remains unclear. This study aimed to evaluate the incidence of subclinical cardiac perforation among various CIED leads using cardiac computed tomography (CT). METHODS: A total of 271 consecutive patients with 463 CIED leads, who underwent cardiac CT after CIED implantation, were included in this retrospective observational study. Cardiac CT images were reviewed by one radiologist and two cardiologists. Subclinical perforation was defined as traversal of the lead tip past the outer myocardial layer without symptoms and signs related to cardiac perforation. We compared the subclinical cardiac perforation rates of the available lead types. RESULTS: A total of 219, 49, and 3 patients had pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy, respectively. The total subclinical cardiac perforation rate was 5.6%. Subclinical cardiac perforation by screw-in ventricular leads was significantly more frequent than that caused by tined ventricular leads (13.3% vs 3.3%, respectively, p = 0.002). There were no significant differences in the incidence of cardiac perforation between atrial and ventricular leads, screw-in and tined atrial leads, pacing and defibrillator ventricular leads, nor between magnetic resonance (MR)-conditional and MR-unsafe screw-in ventricular leads. Screw-in ventricular leads were significantly associated with subclinical cardiac perforation [odds ratio, 4.554; 95% confidence interval, 1.587-13.065, p = 0.005]. There was no case subclinical cardiac perforation by septal ventricular leads. CONCLUSIONS: Subclinical cardiac perforation by screw-in ventricular leads is not rare. Septal pacing may be helpful in avoiding cardiac perforation.

Usefulness of cardiac magnetic resonance images for prediction of sudden cardiac arrest in patients with mitral valve prolapse: a multicenter retrospective cohort study.

BACKGROUND: An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. METHODS: MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. RESULTS: Of the 85 patients [age, 54.0 (41.0-65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65-148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02-1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08-1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. CONCLUSIONS: The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

Less dementia after catheter ablation for atrial fibrillation: a nationwide cohort study.

AIMS: Accumulating evidence shows that atrial fibrillation (AF) is associated with an increased risk of dementia. Catheter ablation for AF prolongs the duration of sinus rhythm, thereby improving the quality of life. We investigated the association of catheter ablation for AF with the occurrence of dementia. METHODS AND RESULTS: Using the Korean National Health Insurance Service database, among 194 928 adults with AF treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between 1 January 2005 and 31 December 2015, we studied 9119 patients undergoing ablation and 17 978 patients managed with medical therapy. The time-at-risk was counted from the first medical therapy, and ablation was analysed as a time-varying exposure. Propensity score-matching was used to correct for differences between the groups. During a median follow-up of 52 months, compared with patients with medical therapy, ablated patients showed lower incidence and risk of overall dementia (8.1 and 5.6 per 1000 person-years, respectively; hazard ratio 0.73, 95% confidence interval 0.58-0.93). The associations between ablation and dementia risk were consistently observed after additionally censoring for incident stroke (hazard ratio 0.76, 95% confidence interval 0.61-0.95) and more pronounced in cases of ablation success whereas no significant differences observed in cases of ablation failure. Ablation was associated with lower risks of dementia subtypes including Alzheimer's disease and vascular dementia. CONCLUSION: In this nationwide cohort of AF patients treated with catheter ablation or medical therapy, ablation was associated with decreased dementia risk. This relationship was evident after censoring for stroke and adjusting for clinical confounders.

Potential causal association of a prolonged PR interval and clinical recurrence of atrial fibrillation after catheter ablation: a Mendelian randomization analysis.

A prolonged PR interval predicts atrial fibrillation (AF) recurrence after catheter ablation. We investigated the causal association between the PR interval and AF clinical recurrence by a Mendelian randomization. We prospectively included 1722 patients with AF (73.2% male, 58.6 ± 10.8 years old, 71.3% paroxysmal AF) who underwent catheter ablation into a genome-wide association study (GWAS). We searched for the genetic associations between the PR interval and AF recurrence by analyzing 44 single nucleotide polymorphisms (SNPs) already known to be associated with the PR interval, and investigated the Mendelian randomization. Based on the quartile analysis, the highest quartile of the PR interval was associated with an increased risk of AF recurrence compared with the lowest quartile (Hazard ratio (HR) = 1.91, 95% CI = 1.51-2.42, P = 8.41 × 10-8) during 35.7 ± 28.5 months of follow-up. Among 44 SNPs known to be associated with the PR interval, two SNPs had significant associations with the PR interval (P < 0.001 for each SNP). CAV1 (HR = 1.15, 95% CI = 1.02-1.31, P = 0.024) was associated with clinical recurrence of AF. A Mendelian randomization analysis demonstrated a significant association with CAV1 (HR = 1.04, 95% CI = 1.01-1.07, P = 0.006). A prolonged PR interval was a risk factor for an AF recurrence, and the PR interval had a potentially causal association with an AF clinical recurrence after catheter ablation at the genetic level.

Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation.

INSTRUCTION: Longer atrial fibrillation (AF) durations have higher recurrence rates after rhythm control. However, there is limited data on the effect of the AF duration on recurrence after atrial fibrillation catheter ablation (AFCA). In the present study, we investigated the rhythm outcome of AFCA according to the AF duration based on the first electrocardiogram (ECG) diagnosis. METHODS AND RESULTS: We included 1005 patients with AF (75% male, 59 ± 11 years old) who underwent AFCA and whose first ECG diagnosis time point was evident. The clinical characteristics and rhythm outcomes were compared based on the AF duration (≤3 years, n = 537; >3 years, n = 468) and AF burden (paroxysmal atrial fibrillation [PAF], n = 387; persistent atrial fibrillation [PeAF], n = 618). Longer AF durations were associated with older age (P = .020), larger left atrial size (P = .009) and a higher number of patients with hypertension (P < .001) or PeAF (P < .001). During 24 ± 22 months of follow-up, the postablation clinical recurrence rate was higher in patients with a longer AF duration (logrank P = .002). The AF recurrence rate was significantly higher in PeAF patients with an AF duration >3 years (logrank P = 0.009), but not in subjects with PAF (logrank P = .939). In a multivariate Cox regression analysis, a longer AF duration was significantly associated with a higher clinical recurrence rate after AFCA in PeAF patients (adjusted hazard ratio, 1.06; range, 1.03-0.10; P = 0.001), but not PAF. CONCLUSION: Although longer AF duration was associated with higher clinical recurrence rates after AFCA, the rate was significant in patients with PeAF lasting >3 years, but not in PAF patients.