Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.

P wave duration ≥150 ms predicts poor left atrial function and ablation outcomes in non-paroxysmal atrial fibrillation.

BACKGROUND: It remains unknown whether P wave duration (PWD) ≥ 150 ms measured after extensive radiofrequency catheter ablation (RFCA) can identify non-paroxysmal atrial fibrillation (non-PAF) patients at increased risk of atrial tachyarrhythmia recurrence. We investigated the predicting power of PWD and its association with left atrial (LA) reverse remodeling in patients with non-PAF undergoing pulmonary vein isolation with LA linear ablation. METHODS: We retrospectively evaluated 136 patients who underwent RFCA for drug-refractory non-PAF. Electroanatomic mapping was acquired during AF. Low-voltage area (LVA) was defined as an area with bipolar voltage ≤0.5 mV. Electrocardiography and echocardiography were performed during sinus rhythm 1 day and 3 months after RFCA. PWD was measured using amplified 12­lead electrocardiography. Prolonged PWD was defined as maximum PWD ≥ 150 ms. RESULTS: Over a mean follow-up duration of 48 ± 35 months, 28 patients experienced atrial tachyarrhythmia recurrence. PWD was positively correlated with LVA (r = 0.527, p < 0.001) and inversely correlated with LA emptying fraction (r = -0.399, p < 0.001). PWD was shortened and LA emptying fraction (LAEF) was increased in patients without atrial tachyarrhythmia recurrence during follow-up. Atrial tachyarrhythmia-free survival was significantly more likely in patients without a prolonged PWD (83.5% vs 60.7%, p = 0.002). Multivariate analysis showed that LAEF and PWD were independent predictors of atrial tachyarrhythmia recurrence. CONCLUSIONS: PWD ≥ 150 ms measured after RFCA can identify patients with non-PAF at increased risk of atrial tachyarrhythmia recurrence. PWD is correlated with LVA and LAEF and reflects LA reverse remodeling.

Sacubitril/Valsartan Therapy Ameliorates Ventricular Tachyarrhythmia Inducibility in a Rabbit Myocardial Infarction Model.

BACKGROUND: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model. METHODS AND RESULTS: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. CONCLUSIONS: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility.

Single Bolus Rosuvastatin Accelerates Calcium Uptake and Attenuates Conduction Inhomogeneity in Failing Rabbit Hearts With Regional Ischemia-Reperfusion Injury.

Acute statin therapy reduces myocardial ischemia/reperfusion (IR) injury-induced ventricular fibrillation (VF), but the underlying electrophysiological mechanisms remain unclear. This study sought to investigate the antiarrhythmic effects of a single bolus rosuvastatin injection in failing rabbit hearts with IR injury and to unveil the underlying molecular mechanisms. Rabbits were divided into rosuvastatin, rosuvastatin + L-NAME, control, and L-NAME groups. Intravenous bolus rosuvastatin (0.5 mg/kg) and/or L-NAME (10 mg/kg) injections were administered 1 hour and 15 minutes before surgery, respectively. Heart failure was induced using rapid ventricular pacing. Under general anesthesia with isoflurane, an IR model was created by coronary artery ligation for 30 minutes, followed by reperfusion for 15 minutes. Plasma NO end product levels were measured during IR. Then, hearts were excised and Langendorff-perfused for optical mapping studies. Cardiac tissues were sampled for Western blot analysis. Rosuvastatin increased plasma NO levels during IR, which was abrogated by L-NAME. Spontaneous VF during IR was suppressed by rosuvastatin (P < 0.001). Intracellular calcium (Cai) decay and conduction velocity were significantly slower in the IR zone. Rosuvastatin accelerated Cai decay, ameliorated conduction inhomogeneity, and reduced the inducibility of spatially discordant alternans and VF significantly. Western blots revealed significantly higher expression of enhancing endothelial NO-synthase and phosphorylated enhancing endothelial NO-synthase proteins in the Rosuvastatin group. Furthermore, SERCA2a, phosphorylated connexin43, and phosphorylated phospholamban were downregulated in the IR zone, which was attenuated or reversed by rosuvastatin. Acute rosuvastatin therapy before ischemia reduced IR-induced VF by improving SERCA2a function and ameliorating conduction disturbance in the IR zone.

Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs.

Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular and functional features, and drug response of cardiomyocytes (PSC-CMs) and endothelial cells (PSC-ECs) derived from genetically relevant sets of human iPSCs, SCNT-derived embryonic stem cells (nt-ESCs), as well as in vitro fertilization embryo-derived ESCs (IVF-ESCs). We found that differentiated cells derived from isogenic iPSCs and nt-ESCs showed comparable lineage gene expression, cellular heterogeneity, physiological properties, and metabolic functions. Genome-wide transcriptome and DNA methylome analysis indicated that iPSC derivatives (iPSC-CMs and iPSC-ECs) were more similar to isogenic nt-ESC counterparts than those derived from IVF-ESCs. Although iPSCs and nt-ESCs shared the same nuclear DNA and yet carried different sources of mitochondrial DNA, CMs derived from iPSC and nt-ESCs could both recapitulate doxorubicin-induced cardiotoxicity and exhibited insignificant differences on reactive oxygen species generation in response to stress condition. We conclude that molecular and functional characteristics of differentiated cells from human PSCs are primarily attributed to the genetic compositions rather than the reprogramming mechanisms (SCNT vs. iPSCs). Therefore, human iPSCs can replace nt-ESCs as alternatives for generating patient-specific differentiated cells for disease modeling and preclinical drug testing.

Conjunction of Endocardial and Coronary Venous System Mapping to Ablate Ventricular Arrhythmias.

BACKGROUND: Ablation of idiopathic ventricular arrhythmias (VAs) with epicardial or intramural origins is technically challenging. Herein, we have described the successful ablation of left VAs via the coronary venous system (CVS) in conjunction with endocardial map guided by three-dimensional electroanatomical map in six patients. METHODS: Out of a total consecutive 84 patients with symptomatic idiopathic VAs, radiofrequency ablation via the CVS was performed on six patients (7%). Furthermore, we reviewed patient records and electrophysiologic studies with respect to clinical characteristics. RESULTS: Activation map was conducted in 5 patients, and the earliest activation sites were identified within the CVS. The preceding times to the onset of QRS complex were longer than those at the earliest endocardial sites (36.2 ± 5.6 ms vs. 14.2 ± 6.4 ms, p = 0.02, n = 5). Spiky fractionated long-duration potentials were recorded at the successful ablation sites in all 5 patients. The other patient received pacemapping only because of few spontaneous VAs during the procedure, and the best pacemap spot was found within the CVS. Irrigated catheters were required in 4 out of 6 patients because VAs were temporarily suppressed with regular ones. CONCLUSIONS: Idiopathic VAs can be ablated via the CVS in conjunction with endocardial mapping. Additionally, spiky fractionated long-duration potential can function as a clue to identify the good ablation site.

The circadian rhythm controls telomeres and telomerase activity.

Circadian clocks are fundamental machinery in organisms ranging from archaea to humans. Disruption of the circadian system is associated with premature aging in mice, but the molecular basis underlying this phenomenon is still unclear. In this study, we found that telomerase activity exhibits endogenous circadian rhythmicity in humans and mice. Human and mouse TERT mRNA expression oscillates with circadian rhythms and are under the control of CLOCK-BMAL1 heterodimers. CLOCK deficiency in mice causes loss of rhythmic telomerase activities, TERT mRNA oscillation, and shortened telomere length. Physicians with regular work schedules have circadian oscillation of telomerase activity while emergency physicians working in shifts lose the circadian rhythms of telomerase activity. These findings identify the circadian rhythm as a mechanism underlying telomere and telomerase activity control that serve as interconnections between circadian systems and aging.

Dantrolene suppresses ventricular ectopy and arrhythmogenicity with acute myocardial infarction in a langendorff-perfused pacing-induced heart failure rabbit model.

INTRODUCTION: Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking. METHODS AND RESULTS: HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 µM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed. CONCLUSION: In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility.

Remote past left ventricular function before chronic right ventricular pacing predicts responses to cardiac resynchronization therapy upgrade.

BACKGROUND: This study examined factors that could predict response to cardiac resynchronization therapy (CRT) upgrade in patients who developed heart failure (HF) after long-term right ventricular (RV) pacing. METHODS: Twenty-five consecutive patients who received CRT upgrade for long-term RV pacing (RVP) were enrolled in this study. None of these patients were eligible for CRT at the moment of starting RVP. After 5.7 ± 4.0 years chronic RVP, these 25 patients developed HF symptoms and received CRT upgrade. Echocardiography was conducted at the moment of CRT upgrade and 6 months after CRT. Remote past left ventricular ejection fraction (RP-LVEF) at the moment of starting RVP was retrospectively obtained from the echocardiographic and cardiac catherization reports. Responders were defined as a reduction in LV end-systolic volume (LVESV) ≥ 15%. Their clinical and echocardiographic parameters were analyzed and compared. RESULTS: Responders had significant higher RP-LVEF as compared to nonresponders (53.6 ± 16.5% vs 31.4 ± 11.6%, P = 0.002). RP-LVEF correlated with reduction in LVESV after CRT upgrade (P < 0.001). RP-LVEF ≥ 43.5% as a cutoff value predicted response to CRT upgrade with an area under the receiver-operating curve of 0.87, a sensitivity of 78%, and a specificity of 100%. Intrinsic QRS width, septal-posterior wall motion delay, or tissue Doppler-derived dyssynchrony indexes did not predict responses to CRT upgrade. CONCLUSION: In long-term RVP patients who developed HF and received CRT upgrade, RP-LVEF ≥ 43.5% predicts good response. Conventional dyssynchrony indexes do not predict responses to CRT upgrade in these patients.

Contrasting effects of HMR1098 on arrhythmogenicity in a Langendorff-perfused phase-2 myocardial infarction rabbit model.

BACKGROUND: The stability of dynamic factors has been reported to play a role in the antiarrhythmic actions of adenosine triphosphate (ATP)-sensitive potassium channel (KATP) opener in phase-2 myocardial infarction (MI) hearts. In the situation of the downregulation of KATP, the effects of KATP blocker (HMR1098) on the dynamic factors and electrophysiological changes during phase-2 MI remain unclear. METHODS: Dual voltage and intracellular Ca(2+) (Cai) optical mapping was performed in nine Langendorff-perfused hearts 4-5 hours after coronary artery ligation and five control hearts. Electrophysiology studies, including action potential duration (APD) restitution, conduction velocity (CV), inducibility of ventricular fibrillation (VF), VF dominant frequency, APD and Cai alternans, and Cai decay, were performed. The same protocol was repeated in the presence of HMR1098 (10 µm) after the baseline studies. RESULTS: HMR1098 significantly prolonged APD and effective refractory period to prevent sustained VF in five of nine MI hearts and two of five control hearts compared to none at baseline in both groups. On the other hand, HMR1098 steepened APD restitution slope to enhance spatially concordant alternans in both groups. In the phase-2 MI group, HMR1098 steepened CV restitution slope and enhanced spatially discordant alternans (SDA), which might account for a decreased pacing threshold of VF induction during HMR1098 infusion in phase-2 MI hearts. CONCLUSIONS: In phase-2 MI hearts, HMR1098 has contrasting effects on arrhythmogenesis, suppressing reentry and VF persistence but facilitating VF inducibility. The mechanism is the intensified induction of SDA because of the steepened APD and CV restitution slopes.

Successful treatment of macroreentrant atrial tachycardia by radiofrequency ablation targeting channels with continuous activation.

BACKGROUND: Macroreentrant atrial tachycardia (MRAT) is frequently unresponsive to antiarrhythmic drugs. The application of three-dimensional (3D) mapping and entrainment pacing contributes to a high success rate for radiofrequency ablation, but programmed electrical pacing may either terminate or transform clinical tachyarrhythmias. On the basis of clinical experiences of the use of ventricular tachycardia ablation, channels with continuous activation are suitable for reentrant circuits, and ablation at these channels can lead to noninducibility of ventricular tachycardias. We reviewed patients referred for symptomatic MRAT with identified channels with continuous activation and evaluated the efficacy of MRAT ablation by targeting these channels. METHODS: Fifteen consecutive patients (10 men, 49 ± 14 years) with MRAT illustrated by endocardial activation maps using a 3D electroanatomical mapping system (CARTO™, Biosense Webster, Diamond Bar, CA, USA) were included in this study. Continuous activation was defined as double or continuous potentials without an isoelectric interval, and sites with continuous activation were tagged for measurements of channel properties. Radiofrequency ablation was performed at those targeted sites located within the reentrant circuit. RESULTS: Radiofrequency ablation successfully eliminated MRAT in all patients. The mean cycle length was 283 ± 60 ms, and the longest activation duration was 112 ± 38 ms. The minimal and maximal bipolar voltage amplitudes were 0.13 ± 0.1 mV and 0.7 ± 0.6 mV, respectively. The targeted ablation length and width were 28.9 ± 15.3 mm and 9.4 ± 3.3 mm, respectively. CONCLUSION: Radiofrequency ablation of MRAT targeting channels with continuous activation using a 3D electroanatomical mapping system yields a high success rate.

Long-Term Survival of Multicenter Automatic Defibrillator Implantation Trial (MADIT) II-Eligible Patients in Taiwan.

BACKGROUND: he Multicenter Automatic Defibrillator Implantation Trial (MADIT) II showed that use of a prophylactic implantable cardioverter defibrillator (ICD) improved the survival of patients with poor left ventricular ejection fraction after myocardial infarction. The major concerns about primary ICD prevention in Asian countries are the long-term survival and the incidence of sudden cardiac death. Whether long-term outcomes within the Taiwanese population are comparable to the MADIT II trial remains unclear. METHODS: We retrospectively reviewed the clinical records of 1909 inpatients who had both myocardial infarction and heart failure in the discharge diagnoses from Jan. 2001 through Dec. 2006, and 313 patients without ICD implantation who satisfied the MADIT II criteria were included for survival analysis. RESULTS: After 4.60 ± 4.31 years of follow-up, 152 (49%) patients had died. Of these patients, 68 (45%) died of sudden cardiac death, similar to the conventional group (patients without ICD implantation) in the MADIT II study (51%). The Kaplan-Meier curve showed that survival during the first two years in this cohort was inferior to the conventional group of the MADIT II population. After two years, the survival curve was similar to the conventional group but still inferior to the defibrillator group in the MADIT II study. Multivariate Cox regression analysis showed old age and blood urea nitrogen > 25 mg/dL were independent predictors of mortality. A history of percutaneous coronary intervention was associated with lower mortality. CONCLUSIONS: The long-term outcomes of Taiwanese patients who are eligible within MADIT II criteria are similar to the conventional group in the MADIT II study. KEY WORDS: Heart failure; Implantable cardioverter defibrillator; Myocardial infarction; Sudden cardiac death.

Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Comparing Artificial Intelligence-Enabled Electrocardiogram Models in Identifying Left Atrium Enlargement and Long-term Cardiovascular Risk.

BACKGROUND: The role of P-wave in identifying left atrial enlargement (LAE) with the use of artificial intelligence (AI)-enabled electrocardiography (ECG) models is unclear. It is also unknown if AI-enabled single-lead ECG could be used as a diagnostic tool for LAE surveillance. We aimed to build AI-enabled P-wave and single-lead ECG models to identify LAE using sinus rhythm (SR) and non-SR ECGs, and compare the prognostic ability of severe LAE, defined as left atrial diameter ≥ 50 mm, assessed by AI-enabled ECG models vs echocardiography. METHODS: This retrospective study used data from 382,594 consecutive adults with paired 12-lead ECG and echocardiography performed within 2 weeks of each other at Chang Gung Memorial Hospital. UNet++ was used for P-wave segmentation. ResNet-18 was used to develop deep convolutional neural network-enabled ECG models for discriminating LAE. External validation was performed with the use of data from 11,753 patients from another hospital. RESULTS: The AI-enabled 12-lead ECG model outperformed other ECG models for classifying LAE, but the single-lead ECG models also showed excellent performance at a left atrial diameter cutoff of 50 mm. AI-enabled ECG models had excellent and fair discrimination on LAE using the SR and the non-SR data set, respectively. Severe LAE identified by AI-enabled ECG models was more predictive of future cardiovascular disease than echocardiography; however, the cumulative incidence of new-onset atrial fibrillation and heart failure was higher in patients with echocardiography-severe LAE than with AI-enabled ECG-severe LAE. CONCLUSIONS: P-Wave plays a crucial role in discriminating LAE in AI-enabled ECG models. AI-enabled ECG models outperform echocardiography in predicting new-onset cardiovascular diseases associated with severe LAE.

Blunted proarrhythmic effect of nicorandil in a Langendorff-perfused phase-2 myocardial infarction rabbit model.

BACKGROUND: Nicorandil (a K(ATP) opener) administration is reported to reduce ventricular arrhythmias 4.8 ± 2.2 hours after myocardial infarction (MI). The electrophysiological changes and the effects on dynamic factors and dynamically induced spatially discordant alternans by nicorandil during phase-2 MI are unclear. METHODS: Simultaneous voltage and intracellular Ca(2+) (Ca(i)) optical mapping was performed in nine Langendorff-perfused hearts 4-5 hours after coronary artery ligation and nine control hearts. Action potential duration (APD) restitution was constructed and arrhythmogenic alternans was induced by dynamic pacing. Western blot studies (Kir6.1 and Kir6.2) were performed in six more hearts for both groups. Nicorandil (100 µM) was administered after baseline studies. RESULTS: Phase-2 MI hearts showed longer APD, slower conduction velocity (CV), and higher ventricular fibrillation (VF) inducibility than the control hearts. Nicorandil shortened and restored APD without significant arrhythmogenic effects, and also increased the rate of Ca(i) reuptake and flattened CV restitution to suppress spatially discordant alternans, which might account for a tendency toward higher VF threshold with nicorandil infusion in phase-2 MI hearts. Immunoblotting studies showed significant down-regulation of K(ATP) protein expression, which was functionally correlated to the blunted APD shortening response to nicorandil. CONCLUSIONS: K(ATP) expression is down-regulated in phase-2 MI hearts. Nicorandil restores APD, increases the rate of Ca(i) reuptake, and flattens CV restitution to suppress spatially discordant alternans induction, which ameliorates its proarrhythmic effects during phase-2 MI.

Risk factors of recurrence and complication in radiofrequency catheter ablation of atrioventricular reentrant tachycardia in children and adolescents.

BACKGROUND: To compare potential risk factors for complications and recurrence after radiofrequency catheter ablation in symptomatic atrioventricular reentrant tachycardia in children and adolescents. METHODS: We retrospectively reviewed the data of 213 consecutive patients with symptomatic atrioventricular reentrant tachycardia who underwent both electrophysiological study and radiofrequency catheter ablation, divided these patients into two groups, children (age < 12 years) and adolescents (12 < or = rage, 18 years), and compared the location of the accessory pathway, success rate, recurrence rate, complications, presence of congenital heart disease, presence of intermittent ventricular pre-excitation, and presence of Wolff­Parkinson­White syndrome in the two groups. RESULTS: The position of the accessory pathway was mostly right sided in children (61.3%) and left sided in adolescents (61.5%). Children had significantly more congenital heart disease than adolescents (6.4% versus 0.8%). Univariate analysis showed children or adolescents with right-sided accessory pathways to be 6.84 times and those with accessory pathways on both sides of the septum 25 times more likely to relapse than those with a single accessory pathway. Multivariate analysis indicated that children or adolescents with two accessory pathways were six times, and those with intermittent ventricular pre-excitation nine times more at risk of relapsing following radiofrequency ablation than those with single accessory pathways. All five complications occurred in children. CONCLUSIONS: The findings suggest that the position and number of accessory pathways and presence of intermittent ventricular pre-excitation are related to risks of recurrence of atrioventricular reentrant tachycardia in children and adolescents.

Obstetric and fetal/neonatal outcomes in pregnant women with frequent premature ventricular complexes and structurally normal heart.

BACKGROUND: High premature ventricular complex (PVC) burden may increase the risk of left ventricular dysfunction and all-cause mortality. We aimed to evaluate maternal and neonatal outcomes of pregnant women with structurally normal heart having PVC burden ≥1%. METHODS: This retrospective cohort study used data from Chang Gung Research Database. Pregnancies from January 1, 2005, through June 30, 2020, with documented maternal PVC burden ≥1% by 24-h Holter monitor were identified. Pregnant women with a diagnosis of structural heart disease or arrhythmias other than PVC were excluded. We used propensity score matching (PSM) to balance the covariates between the PVC group and normal control group. The PVC group was classified into low-PVC (<10%) and high-PVC burden subgroups. The maternal and neonatal outcomes were assessed through 6 months after delivery or termination. RESULTS: After PSM, there were 214, 61, and 46 pregnant women enrolled in the normal control group, low-PVC burden, and high-PVC burden subgroups, respectively. The high-PVC and low-PVC burden subgroups had composite adverse maternal and neonatal events similar to the control group without use of antiarrhythmic drugs (AADs), but a higher proportion of placental abruption was observed in the high-PVC burden subgroup. Maternal age, diabetes, and overweight were significant predictors of composite adverse maternal events, whereas only maternal age was a significant predictor of composite adverse neonatal events. CONCLUSIONS: High PVC burden was not associated with poor composite adverse maternal and neonatal outcomes with no need of AADs therapy in pregnant women with structurally normal heart.

Long-term efficacy of sodium-glucose cotransporter 2 inhibitor therapy in preventing atrial fibrillation recurrence after catheter ablation in type 2 diabetes mellitus patients.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce new-onset atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We aimed to determine the long-term effects of SGLT2i on atrial tachyarrhythmia recurrence after catheter ablation (CA) in T2DM patients. Methods: This retrospective study enrolled consecutive patients with T2DM undergoing CA for AF between January 2016 and December 2021. Patient baseline demographic characteristics and use of anti-diabetic and anti-arrhythmic medications were analyzed. Echocardiographic parameters were obtained one day and 6 months after CA. Results: Our study population comprised 122 patients (70% paroxysmal AF). The baseline patient characteristics were similar between the SGLT2i-treated group (n = 45) and the non-SGLT2i-treated group (n = 77) except for stroke. At 6-month follow-up, body-mass index (BMI) was significantly decreased and left ventricular ejection fraction (LVEF) was significantly increased only in the SGLT2i group. E/e' was decreased 6 months after CA in both groups. During a mean follow-up of 33.7 ± 21.6 months, 22 of 122 patients had atrial tachyarrhythmia recurrence. The long-term atrial tachyarrhythmia-free survival rate was significantly higher in the SGLT2i-treated patients, and multivariate analysis revealed that AF type and SGLT2i use were independently associated with atrial tachyarrhythmia recurrence after CA. Conclusion: The use of SGLT2i and AF type were independent risk factors associated with atrial tachyarrhythmia recurrence after CA in T2DM patients with AF. This result was at least partly due to the pleiotropic effects of SGLT2i on BMI reduction and left ventricular function improvement.