Efficacy and safety of a novel temperature-controlled catheter for cavotricuspid isthmus ablation.

BACKGROUND: Maintaining an adequate temperature at the target site is essential for effective ablation. We hypothesized that a tissue temperature-controlled (T-Con) catheter for cavotricuspid isthmus (CTI) ablation could improve the procedural ablation parameters. PURPOSE: To evaluate the efficacy and safety of the T-Con (DiamondTemp™) catheter for CTI ablation compared with non-irrigation (Non-Irri) and irrigation (Irri) catheters. METHODS: We analyzed 150 patients who underwent prophylactic CTI ablation combined with pulmonary vein isolation. The Non-Irri, Irri, and T-Con catheter groups comprised 50 patients each, and the ablation procedural parameters and complications were compared between these groups. RESULTS: There were no significant differences in clinical background characteristics among the three groups. The Kruskal-Wallis and post hoc tests demonstrated that the T-Con group showed the lowest total radiofrequency energy delivery time among the three groups (median [25 and 75 percentiles]: 340 [209, 357], 147 [100, 199], and 83 [61, 109] s, respectively in the Non-Irri, Irri, and T-Con groups; T-Con versus Non-Irri, p < .01; T-Con versus Irri, p < .01). The total procedural time and acute reconnection rate in the T-Con group (264 s and 4%, respectively) were lower than those in the Non-Irri group (438 s and 24%) but were similar to those in the Irri group (268 s and 6%). No significant complications were observed in any group. CONCLUSIONS: The T-Con catheter achieved a short energy delivery time and a low acute reconnection rate, indicating its potential as an alternative catheter for CTI ablation.

Wide Spectrum of Bradyarrhythmias and Supraventricular Tachyarrhythmias in Sportsmen: Run Forrest, Run?!

The intricate relationship between sports participation and cardiac arrhythmias is a key focus of cardiovascular research. Physical activity, integral to preventing atherosclerotic cardiovascular disease, induces structural, functional, and electrical changes in the heart, potentially triggering arrhythmias, particularly atrial fibrillation (AF). Despite the cardiovascular benefits, the optimal exercise amount remains unclear, revealing a J-shaped association between AF and exercise. Endurance athletes, particularly males, face elevated AF risks, influenced by age. Risk factors vary among sports modalities, with unique physiological responses in swim training potentially elevating AF risk. Clinical management of AF in athletes necessitates a delicate balance between rhythm control, rate control, and anticoagulation therapy. Sport-induced bradyarrhythmias, including sinus bradycardia and conduction disturbances, are prevalent among athletes. Managing bradycardia in athletes proves challenging due to its complex and not fully understood pathophysiology. Careful consideration is required, particularly in symptomatic cases, where pacemaker implantation may be necessary for sinus node dysfunction. Although pacing is recommended for specific atrioventricular (AV) blocks, milder forms often prevail without restricting sports participation. This review explores the nuanced relationship between exercise and tachy- and bradyarrhythmia in athletes, addressing the challenges clinicians face when optimizing patient care in this distinctive population.

Implantable Cardiac Devices in Patients with Brady- and Tachy-Arrhythmias: An Update of the Literature.

Implantable cardiac devices are a vital treatment option in the management of tachy/brady-arrhythmias and heart failure with conduction disease. In the recent years, these devices have become increasingly sophisticated, with high implantation success rates and longevity. However, these devices are not without risks and complications, which need to be carefully considered before implantation. In an era of rapidly evolving cardiac device therapies, this review article will provide an update on the literature and outline some of the emerging technologies that aim to maximise the efficiency of implantable devices and reduce complications. We discuss novel pacing techniques, including alternative pacing sites in anti-bradycardia and biventricular pacing, as well as the latest evidence surrounding leadless device technologies and patient selection for implantable device therapies.

Histological and functional assessment of a Takotsubo cardiomyopathy model established by immobilization stress.

INTRODUCTION: Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, resembles acute heart failure syndrome but lacks disease-specific diagnosis and treatment strategies. TTC accounts for approximately 5-6% of all suspected cases of acute coronary syndrome in women. At present, animal models of TTC are often created by large amounts of exogenous catecholamines such as isoproterenol. However, isoproterenol injection cannot fully simulate the onset of stress-induced cardiomyopathy in humans since stress is not an instantaneous event. METHODS: Rats were immobilized for 6 h per day for 1-14 days. To examine whether the TTC model was successful, echocardiography was employed; Elisa detected serum sympathetic activation markers; and the Open-Field test (OFT) was used to analyze behavioral changes in rats after stress. Western blot and histology were used to assess sympathetic remodeling, inflammation levels, and fibrosis; qRT-PCR was used to explore the levels of fibrosis and myocardial hypertrophy. The electrical stability of ventricular was determined by electrophysiological testing. RESULTS: The rats showed severe stress behavior and local sympathetic remodeling of the heart after only 1 day of stress. After 3 days of stress, the induction of ventricular tachyarrhythmia increased prominently. The highest incidence of TTC in rats was at 5 days of immobilization stress. The pathological left ventricular remodeling caused by immobilization (IMO) stress includes inflammatory infiltration, fibrosis, and myocardial hypertrophy. CONCLUSIONS: Our study confirms the hypothesis that IMO stress can mimic Takotsubo cardiomyopathy, and the various effects on the heart depending on the duration of IMO stress. We observed the highest incidence of TTC occurred after 5 days of stress. Furthermore, there is a gradual occurrence of electrical and structural remodeling as the stress duration prolongs.

Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L-type Ca+ current.

OBJECTIVE: To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). METHODS AND RESULTS: Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli-extra-stimulus (S1-S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol-12-myristate-13-acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch-clamp, peak amplitude of L-type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans. CONCLUSION: PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.

Comparative analysis of recurrence predictors and outcomes for atrial tachyarrhythmia following atrial fibrillation ablation: high-power short-duration vs. conventional pulmonary vein isolation.

Atrial fibrillation (AF) is a common cardiac arrhythmia, with structural and electrical remodeling being significant risk factors for recurrence post-catheter ablation. The advent of high-power short-duration pulmonary vein isolation (HPSD-PVI) presents a novel approach, potentially enhancing procedural success rates through the creation of transmural lesions without overheating. This study investigates the predictors of atrial tachyarrhythmia (ATA) recurrence and compares outcomes between HPSD-PVI and conventional PVI techniques. A total of 1005 patients undergoing radiofrequency catheter ablation (RFA) for AF were retrospectively analyzed in this study. The cohort was divided based on the ablation strategy: conventional PVI from February 2013 to September 2018, and HPSD-PVI from October 2018 onwards. The primary objective was to compare the predictors of ATA recurrence and the outcome between the two groups. Among 969 patients analyzed after exclusions, independent predictors of recurrence differed between groups; higher CHADS2/CHA2DS2-VASc scores and lower left ventricular ejection fraction (LVEF) were significant in the HPSD-PVI group, while non-paroxysmal AF, larger left atrial volume index (LAVI), and longer AF history were predictors in the conventional PVI group. The HPSD-PVI group showed a trend toward lower ATA recurrence rates compared to the conventional PVI group in the propensity-score-matched (PSM) cohort (log-rank test, p = 0.06). Higher CHADS2/CHA2DS2-VASc scores and lower LVEF were also independent predictors of ATA recurrence in the PSM cohort.

RyR2 C-terminal truncating variants identified in patients with arrhythmic phenotypes exert a dominant negative effect through formation of wildtype-truncation heteromers.

Gain-of-function missense variants in the cardiac ryanodine receptor (RyR2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), whereas RyR2 loss-of-function missense variants cause Ca2+ release deficiency syndrome (CRDS). Recently, truncating variants in RyR2 have also been associated with ventricular arrhythmias (VAs) and sudden cardiac death. However, there are limited insights into the potential clinical relevance and in vitro functional impact of RyR2 truncating variants. We performed genetic screening of patients presenting with syncope, VAs, or unexplained sudden death and in vitro characterization of the expression and function of RyR2 truncating variants in HEK293 cells. We identified two previously unknown RyR2 truncating variants (Y4591Ter and R4663Ter) and one splice site variant predicted to result in a frameshift and premature termination (N4717 + 15Ter). These 3 new RyR2 truncating variants and a recently reported RyR2 truncating variant, R4790Ter, were generated and functionally characterized in vitro. Immunoprecipitation and immunoblotting analyses showed that all 4 RyR2 truncating variants formed heteromers with the RyR2-wildtype (WT) protein. Each of these C-terminal RyR2 truncations was non-functional and suppressed [3H]ryanodine binding to RyR2-WT and RyR2-WT mediated store overload induced spontaneous Ca2+ release activity in HEK293 cells. The expression of these RyR2 truncating variants in HEK293 cells was markedly reduced compared with that of the full-length RyR2 WT protein. Our data indicate that C-terminal RyR2 truncating variants are non-functional and can exert a dominant negative impact on the function of the RyR2 WT protein through formation of heteromeric WT/truncation complex.

Tachyarrhythmia after the total cavopulmonary connection: incidence, prognosis, and risk factors.

OBJECTIVE: The purpose of this study is to evaluate the incidence and outcomes regarding tachyarrhythmia in patients after total cavopulmonary connection. METHODS: A retrospective analysis of 620 patients who underwent total cavopulmonary connection between 1994 and 2021 at our institution was performed. Incidence of tachyarrhythmia was depicted, and results after onset of tachyarrhythmia were evaluated. Factors associated with the onset of tachyarrhythmia were identified. RESULTS: A total of 52 (8%) patients presented with tachyarrhythmia that required medical therapy. Onset during hospital stay was observed in 27 patients, and onset after hospital discharge was observed in 32 patients. Freedom from late tachyarrhythmia following total cavopulmonary connection at 5, 10, and 15 years was 97, 95, and 91%, respectively. The most prevalent late tachyarrhythmia was atrial flutter (50%), followed by supraventricular tachycardia (25%) and ventricular tachycardia (25%). Direct current cardioversion was required in 12 patients, and 7 patients underwent electrophysiological study. Freedom from Fontan circulatory failure after onset of tachyarrhythmia at 10 and 15 years was 78% and 49%, respectively. Freedom from occurrence of decreased ventricular systolic function after the onset of tachyarrhythmia at 5 years was 85%. Independent factors associated with late tachyarrhythmia were dominant right ventricle (hazard ratio, 2.52, p = 0.02) and weight at total cavopulmonary connection (hazard ratio, 1.03 per kilogram; p = 0.04). Type of total cavopulmonary connection at total cavopulmonary connection was not identified as risk. CONCLUSIONS: In our large cohort of 620 patients following total cavopulmonary connection, the incidence of late tachyarrhythmia was low. Patients with dominant right ventricle and late total cavopulmonary connection were at increased risk for late tachyarrhythmia following total cavopulmonary connection.

Antiarrhythmic therapy for narrow QRS supraventricular tachyarrhythmias in newborns and infants in the first year of life: Potent tools to be handled with care.

Supraventricular tachyarrhythmias pose a significant challenge in neonates and infants, particularly within the first year of life, where prompt and effective management is crucial. By synthesizing available evidence and clinical experience, this review aims to provide a comprehensive overview of antiarrhythmic therapy in this vulnerable population, with a focus on narrow QRS supraventricular tachyarrhythmias. This review examines the current understanding of supraventricular tachyarrhythmia management and discusses the challenges associated with antiarrhythmic therapy in newborns and infants during the critical first year of life, evaluating the efficacy and safety of various antiarrhythmic agents commonly utilized in this population, including dosing considerations, adverse effects, and strategies for acute management and prophylactic long-term antiarrhythmic treatment.

Optogenetic termination of atrial tachyarrhythmias by brief pulsed light stimulation.

AIMS: The most efficient way to acutely restore sinus rhythm from atrial fibrillation (AF) is electrical cardioversion, which is painful without adequate sedation. Recent studies in various experimental models have indicated that optogenetic termination of AF using light-gated ion channels may provide a myocardium-specific and potentially painless alternative future therapy. However, its underlying mechanism(s) remain(s) incompletely understood. As brief pulsed light stimulation, even without global illumination, can achieve optogenetic AF termination, besides direct conduction block also modulation of action potential (AP) properties may be involved in the termination mechanism. We studied the relationship between optogenetic AP duration (APD) and effective refractory period (ERP) prolongation by brief pulsed light stimulation and termination of atrial tachyarrhythmia (AT). METHODS AND RESULTS: Hearts from transgenic mice expressing the H134R variant of channelrhodopsin-2 in atrial myocytes were explanted and perfused retrogradely. AT induced by electrical stimulation was terminated by brief pulsed blue light stimulation (470 nm, 10 ms, 16 mW/mm2) with 68% efficacy. The termination rate was dependent on pulse duration and light intensity. Optogenetically imposed APD and ERP changes were systematically examined and optically monitored. Brief pulsed light stimulation (10 ms, 6 mW/mm2) consistently prolonged APD and ERP when light was applied at different phases of the cardiac action potential. Optical tracing showed light-induced APD prolongation during the termination of AT. CONCLUSION: Our results directly demonstrate that cationic channelrhodopsin activation by brief pulsed light stimulation prolongs the atrial refractory period suggesting that this is one of the key mechanisms of optogenetic termination of AT.

Contribution of cytokine-mediated prolongation of QTc interval to the multi-hit theory of Torsade de Pointes.

BACKGROUND: Torsade de pointes is a potentially lethal polymorphic ventricular tachyarrhythmia that can occur in the setting of long QT syndrome (LQTS). LQTS is multi-hit in nature and multiple factors combine their effects leading to increased arrhythmic risk. While hypokalemia and multiple medications are accounted for in LQTS, the arrhythmogenic role of systemic inflammation is increasingly recognized but often overlooked. We tested the hypothesis that the inflammatory cytokine interleukin(IL)-6 will significantly increase the incidence of arrhythmia when combined with other pro-arrhythmic conditions (hypokalemia and the psychotropic medication, quetiapine). METHODS: Guinea pigs were injected intraperitoneally with IL-6/soluble IL-6 receptor and QT changes were measured in vivo. Subsequently, hearts were cannulated via Langendorff perfusion for ex vivo optical mapping measurements of action potential duration (APD90) and arrhythmia inducibility. Computer simulations (MATLAB) were performed to investigate IKr inhibition at varying IL-6 and quetiapine concentrations. RESULTS: IL-6 prolonged QTc in vivo guinea pigs from 306.74 ± 7.19 ms to 332.60 ± 8.75 ms (n = 8, p = .0021). Optical mapping on isolated hearts demonstrated APD prolongation in IL-6- vs saline groups (3Hz APD90:179.67 ± 2.47 ms vs 153.5 ± 7.86 ms, p = .0357). When hypokalemia was introduced, the APD90 increased to 195.8 ± 5.02 ms[IL-6] and 174.57 ± 10.7 ms[saline] (p = .2797), and when quetiapine was added to hypokalemia to 207.67 ± 3.03 ms[IL-6] and 191.37 ± 9.49 ms[saline] (p = .2449). After the addition of hypokalemia ± quetiapine, arrhythmia was induced in 75% of IL-6-treated hearts (n = 8), while in none of the control hearts (n = 6). Computer simulations demonstrated spontaneous depolarizations at ∼83% aggregate IKr inhibition. CONCLUSIONS: Our experimental observations strongly suggest that controlling inflammation, specifically IL-6, could be a viable and important route for reducing QT prolongation and arrhythmia incidence in the clinical setting.

Association of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) with Cardiac Arrhythmias: A Systematic Review and Meta-Analysis of Cardiovascular Outcome Trials.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of widely used hypoglycemic agents for the treatment of type 2 diabetes mellitus (T2DM). In addition to lowering blood glucose, SGLT2i protects the heart and kidney, significantly reduces cardiovascular events, and delays the progression of heart failure and chronic kidney disease. However, previous studies have not exhaustively discussed the association between SGLT2i and the risk of developing cardiac arrhythmias. The purpose of this study is to assess the association of SGLT2i with cardiac arrhythmias in patients with T2DM and without T2DM in cardiovascular outcome trials (CVOTs). Methods: We performed a meta-analysis and systematic review of CVOTs that compared SGLT2i with placebo. MEDLINE, Web of Science, The Cochrane Library and Embase were systematically searched from inception to December 2022. We included CVOTs reporting cardiovascular or renal outcomes with a follow-up duration of at least 6 months. Results: A total of 12 CVOTs with 77,470 participants were included in this meta-analysis (42,016 SGLT2i vs 35,454 control), including patients with T2DM, heart failure (HF), or chronic kidney disease (CKD). Follow-up duration ranged from 9 months to 5.65 years. Medications included empagliflozin, canagliflozin, dapagliflozin and ertugliflozin. SGLT2i were associated with a lower risk of tachycardia (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.79-0.95), supraventricular tachycardia (SVT; RR 0.84; 95% CI 0.75-0.94), atrial fibrillation (AF; RR 0.86; 95% CI 0.75-0.97) and atrial flutter (AFL; RR 0.75; 95% CI 0.57-0.99) in patients with T2DM, HF and CKD. SGLT2i could also reduce the risk of cardiac arrest in CKD patients (RR 0.50; 95% CI 0.26-0.95). Besides, SGLT2i therapy was not associated with a lower risk of ventricular arrhythmia and bradycardia. Conclusions: SGLT2i therapy is associated with significantly reduced the risk of tachycardia, SVT, AF, and AFL in patients with T2DM, HF, and CKD. In addition, SGLT2i could also reduce the risk of cardiac arrest in CKD patients. Further researches are needed to fully elucidate the antiarrhythmic mechanism of SGLT2i.

Abnormal fetal heart rate patterns caused by pathophysiologic processes other than fetal acidemia.

Fetal acidemia is a common final pathway to fetal death, and in many cases, to fetal central nervous system injury. However, certain fetal pathophysiological processes are associated with significant category II or category III fetal heart rate changes before the development of or in the absence of fetal acidemia. The most frequent of these processes include fetal infection and/or inflammation, anemia, fetal congenital heart disease, and fetal central nervous system injury. In the presence of significant category II or category III fetal heart rate patterns, clinicians should consider the possibility of the aforementioned fetal processes depending on the clinical circumstances. The common characteristic of these pathophysiological processes is that their associated fetal heart rate patterns are linked to increased adverse neonatal outcomes despite the absence of acidemia at birth. Therefore, in these cases, the fetal heart rate patterns may provide more insight about the fetal condition and pathophysiology than the acid-base status at birth. In addition, as successful timing of intrapartum interventions on the basis of evolution of fetal heart rate patterns aims to prevent fetal acidemia, it may not be logical to continue to use the fetal acid-base status at birth as the gold standard outcome to determine the predictive ability of category II or III fetal heart rate patterns. A more reasonable approach may be to use the umbilical cord blood acid-base status at birth as the gold standard for determining the appropriateness of the timing of our interventions.

The association of coagulation and atrial fibrillation: a systematic review and meta-analysis.

AIMS: While atrial fibrillation (AF) is suggested to induce a prothrombotic state, increasing thrombotic risk, it is also hypothesized that coagulation underlies AF onset. However, conclusive evidence is lacking. With this systematic review and meta-analysis, we aimed to summarize and combine the evidence on the associations between coagulation factors with AF in both longitudinal and cross-sectional studies. METHODS AND RESULTS: We systematically searched for longitudinal cohort and cross-sectional studies investigating AF and thrombosis. For longitudinal studies, pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. For cross-sectional studies, we determined pooled standardized mean differences (SMDs) and 95% CIs. A total of 17 longitudinal and 44 cross-sectional studies were included. In longitudinal studies, we found significant associations between fibrinogen (HR 1.05, 95% CI 1.00-1.10), plasminogen activator inhibitor 1 (PAI-1) (HR 1.06, 95% CI 1.00-1.12), and D-dimer (HR 1.10, 95% CI 1.02-1.19) and AF incidence. In cross-sectional studies, we found significantly increased levels of fibrinogen (SMD 0.47, 95% CI 0.20-0,74), von Willebrand factor (SMD 0.96, 95% CI 0.28-1.66), P-selectin (SMD 0.31, 95% CI 0.08-0.54), ß-thromboglobulin (SMD 0.82, 95% CI 0.61-1.04), Platelet Factor 4 (SMD 0.42, 95% CI 0.12-0.7), PAI-1 (1.73, 95% CI 0.26-3.19), and D-dimer (SMD 1.74, 95% CI 0.36-3.11) in AF patients, as opposed to controls. CONCLUSION: These findings suggest that higher levels of coagulation factors are associated with prevalent and incident AF. These associations are most pronounced with prevalent AF in cross-sectional studies. Limited evidence from longitudinal studies suggests a prothrombotic state underlying AF development.

Coherent mapping of atrial tachycardias in patients with congenital heart disease.

AIMS: Coherent mapping (CM) uses a new algorithm to identify critical conduction isthmuses of atrial tachycardias (ATs). We analysed our experience of ablation of AT in patients with congenital heart disease (CHD) with this new technology. METHODS AND RESULTS: All patients with CHD who had CM of AT using the high-density mapping PENTARAY™ catheter and three-dimensional electroanatomic mapping system Carto3 between June 2019 and June 2021 were included retrospectively (n = 27). As a control group, 27 patients with CHD and mapping of AT without CM between March 2016 and June 2019 were included. In total, 54 ablation procedures were performed in 42 patients [median age 35 (interquartile range, IQR 30-48) years] and 64 ATs were induced and mapped (thereof 50 AT intraatrial re-entrant tachycardia and 14 AT ectopic AT). The median procedure duration was 180 (120-214) min and median fluoroscopy time was 10 (5.2-14) min. Acute success was 100% (27/27) in the Coherence group and 74% (20/27) in the non-Coherence group (P = 0.01). During follow-up [median 26 (12-45) months], AT recurred in 28/54 patients, thereof 15 patients needed a re-ablation procedure. Log-rank test showed no difference in recurrence rate between the two groups (P = 0.29). Three minor complications occurred (5.5%). CONCLUSION: Mapping of AT in patients with CHD using the PENTARAY™ mapping catheter and the CM algorithm led to excellent acute success. All ATs were possible to map and no complications related to the PENTARAY™ mapping catheter were observed. Thus, the use of the CM algorithm represents a promising tool in patients with CHD and complex AT.

Clinical Significance of Atrial Tachyarrhythmia Duration for Ventricular Arrhythmia in Patients With Cardiac Resynchronization Therapy.

BACKGROUND: Atrial tachyarrhythmias (ATAs) are reportedly associated with ventricular arrhythmias (VAs). However, little is known about the association between ATA duration and the risk of VA. We investigated the relationship between ATA duration and subsequent VA in patients with a cardiac resynchronization therapy defibrillator (CRT-D).Methods and Results: We investigated associations between the longest ATA duration during the first year after cardiac resynchronization therapy (CRT) implantation and VA and VA relevant to ATA (VAATA) in 160 CRT-D patients. ATAs occurred in 63 patients in the first year. During a median follow-up of 925 days from 1 year after CRT implantation, 40 patients experienced 483 VAs. Kaplan-Meier analysis showed a significantly higher risk of VA in patients with than without ATA in the first year (log rank P=0.0057). Hazard ratios (HR) of VA (HR 2.36, 2.10, and 3.04 for ATA >30s, >6 min and >24 h, respectively) and only VAATA (HR 4.50, 5.59, and 11.79 for ATA >30s, >6 min and >24 h, respectively) increased according to the duration of ATA. In multivariate analysis, ATA >24 h was an independent predictor of subsequent VA (HR 2.42; P=0.02). CONCLUSIONS: Patients with ATA >24 h in the first year after CRT had a higher risk of subsequent VA and VAATA. The risk of VA, including VAATA, increased with the longest ATA duration.

Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3-year follow-up of multicenter trial.

OBJECTIVES: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia. METHODS: This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed. RESULTS: Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI. CONCLUSIONS: This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Resolution of severe cardiomyopathy after catheter ablation of an anteroseptal accessory pathway: A case report.

In patients with non-sustained tachyarrhythmias, left ventricular (LV) systolic dysfunction is uncommon. The role of catheter ablation (CA) in asymptomatic patients with tachyarrhythmia remains unclear. We report a 20-year-old patient without sustained tachyarrhythmia with a left ventricular ejection fraction of 20% who underwent radiofrequency catheter ablation (RFCA) of anteroseptal accessory pathway. She achieved normalization of left ventricular systolic function noted on echocardiography performed at 4 weeks post-ablation. Our case highlights significant improvement in LV systolic function after catheter ablation of an "asymptomatic" ventricular pre-excitation. Current guidelines do not endorse ablating asymptomatic patients, but careful follow-up with serial echocardiograms might be warranted. Prophylactic ablation of those patients with clear evidence of LV dyssynchrony or wide left bundle branch pattern and persistent pre-excitation is worth further consideration.

Hemodynamic profile effects of PM101 amiodarone formulation in patients with post-operative tachyarrhythmias.

Amiodarone may be considered for patients with junctional ectopic tachycardia refractory to treatment with sedation, analgesia, cooling, and electrolyte replacements. There are currently no published pediatric data regarding the hemodynamic effects of the newer amiodarone formulation, PM101, devoid of hypotensive agents used in the original amiodarone formulation. We performed a single-center, retrospective, descriptive study from January 2012 to December 2020 in a pediatric ICU. Thirty-three patients were included (22 male and 11 female) between the ages of 1.1 and 1,460 days who developed post-operative junctional ectopic tachycardia or other tachyarrhythmias requiring PM101. Data analysis was performed on hemodynamic parameters (mean arterial pressures and heart rate) and total PM101 (mg/kg) from hour 0 of amiodarone administration to hour 72. Adverse outcomes were defined as Vasoactive-Inotropic Score >20, patients requiring ECMO or CPR, or patient death. There was no statistically significant decrease in mean arterial pressures within the 6 hours of PM101 administration (p > 0.05), but there was a statistically significant therapeutic decrease in heart rate for resolution of tachyarrhythmia (p < 0.05). Patients received up to 25 mg/kg in an 8-hour time for rate control. Average rate control was achieved within 11.91 hours and average rhythm control within 62 hours. There were four adverse events around the time of PM101 administration, with three determined to not be associated with the medication. PM101 is safe and effective in the pediatric cardiac surgical population. Our study demonstrated that PM101 can be used in a more aggressive dosing regimen than previously reported in pediatric literature with the prior formulation.

Transplacental Therapeutic Drug Monitoring in Pregnant Women with Fetal Tachyarrhythmia Using HPLC-MS/MS.

Fetal arrhythmia develops in 0.1-5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed.