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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.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.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.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.

Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD. The combined angiotensin receptor and neprilysin inhibitor (ARNi; tradename Entresto) is the newest commercially available medication for the treatment of heart failure.We reviewed and synthesized the available literature regarding sacubitril/valsartan and its effects on cardiac rhythm. ARNi has been shown to decrease cardiovascular mortality and hospitalization in patients with HF with reduced ejection fraction (HFrEF). Emerging evidence suggests that ARNi also may play a role in reducing arrhythmogenesis and thereby SCD.This review summarizes the current data regarding this ARNi and its potential antiarrhythmic effects.

AIM: To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes.METHODS: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non-SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all-cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest.RESULTS: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non-SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68-0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all-cause mortality (HR 0.61, 95% CI 0.58-0.64), cardiac arrest (HR 0.70, 95% CI 0.63-0.78), incident AF (HR 0.81, 95% CI 0.76-0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88-0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88-0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71-0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88-1.00).CONCLUSION: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias.

The early repolarization pattern (ERp) is an electrocardiographic finding previously associated with arrhythmic risk in adults. The purpose of this study is to evaluate the prevalence and characteristics of ERp in a group of adolescent athletes according to gender. Furthermore, potential associations with clinical, electrocardiographic, and echocardiographic parameters are explored.In this cross-sectional study young athletes (age 18 years) were consecutively enrolled during the annual pre-participation evaluation, undergoing also transthoracic echocardiography assessment from January 2015 to March 2020.The prevalence of ERp was 27% in the whole population. Athletes with ERp were more frequently men practicing endurance sports. Women with ERp showed lower heart rate at rest, greater posterior, and relative ventricular wall thickness than those without ERp. Men with ERp presented higher systolic blood pressure at peak exercise, greater septal wall thickness, and indexed left ventricular mass than those without ERp. Both genders with ERp showed increased QRS voltage and narrower QRS duration. The ERp phenotype in men was more frequently notched with higher amplitude and ascending ST segment. Women's ERp presented more frequently a slurred morphology, especially in the inferior leads, and horizontal ST slope. No differences emerged in the occurrence of arrhythmias at rest and during maximal exercise test between groups, even considering higher risk phenotypes.ERp is an ECG finding compatible with normal cardiac adaptations to training in young athletes. ERp demonstrated gender differences regarding phenotypes previously associated with increased cardiovascular risk, not showing any differences in arrhythmias during maximal exercise test.

The safety and utility of the Advisor™ High-Density Grid mapping catheter (HDGC) in children and congenital heart disease (CHD) patients are not well described.A single-center retrospective cohort study of pediatric and CHD patients undergoing electrophysiology study and ablation to determine the effect of HDGC use on outcomes including complications, fluoroscopy use, procedure duration, acute ablation success, and arrhythmia recurrence.HDGC was used in 74/261 (28.3%) cases. HDGC subjects differed by median age (17 vs. 13 years; p 0.001), weight (68 vs. 50 kg; p 0.001), and prevalence of significant CHD (42% vs. 3%; p 0.001). Arrhythmia substrates were dissimilar: HGDC cases had higher frequencies of intra-atrial re-entrant tachycardia (25.7% vs. 0.5%), atrial flutter (8.1% vs. 1.1%), ectopic atrial tachycardia (13.5% vs. 3.7%), and premature ventricular contractions (9.5% vs. 0.5%), and lower incidences of atrioventricular re-entrant tachycardia (16.2% vs. 46.1%). Complications were rare (n = 5, 1.9%) with no significant difference between groups (p = 1.00). Procedure duration-but not fluoroscopy exposure-was significantly longer in HDGC cases (median 256 vs. 216 min, p 0.001). Acute success was lower (93.2% vs. 99.4%; p = 0.01) and recurrences higher (13.2% vs. 3.8%; p = 0.016) in HDGC compared to non-HDGC cases.HDGC use in children and CHD patients is safe and not associated with higher complication rates. The lower acute success and higher recurrence rates in HDGC cases likely reflect a bias toward HDGC use in more complex arrhythmia substrates rather than less favorable ablation outcomes.

Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is common; up to 50% of patients with DCM have no cause found despite imaging, genetic and biopsy assessments. Treatment remains focused on managing symptoms, reducing the risk of sudden cardiac death and ameliorating the structural and electrical complications of disease progression. In the absence of aetiology-specific treatments, the condition remains associated with a poor prognosis; mortality is approximately 40% at 10 years. The role of immune-mediated inflammatory injury in the development and progression of DCM was first proposed over 30 years ago. Despite the subsequent failures of three large clinical trials of immunosuppressive treatment (ATTACH, RENEWAL and the Myocarditis Treatment Trial), evidence for an abnormal adaptive immune response in DCM remains significant. In this review, we summarise and discuss available evidence supporting immune dysfunction in DCM, with a specific focus on cellular immunity. We also highlight current clinical and experimental treatments. We propose that the success of future immunosuppressive treatment trials in DCM will be dependent on the deep immunophenotyping of patients, to identify those with active inflammation and/or an abnormal immune response who are most likely to respond to therapy.

Ventricular arrhythmias (VAs) are common after left ventricular assist device (LVAD) implantation though data are mixed on whether these events have an impact on mortality.The National Inpatient Sample (NIS) database from 2002-2019 was queried for LVAD implantation admissions. Secondary ICD codes were analyzed to assess for the occurrence of VAs during this admission. Propensity score matching (PSM) was used to control for confounding variables between those with versus without VAs.The NIS database from 2002-2019 contained 43 936 admissions with LVAD implantation. VAs occurred in 19 985 (45.4%) patients. After PSM, the study cohort consisted of 39 989 patients, 19 985 (50.0%) of which had a secondary diagnosis of VA during the admission. When compared to those without VA, those with VA were at no higher risk for in-hospital mortality (adjusted odds ratio 1.011, 99.9% CI 0.956-1.069, p = 0.699). Those with a VA were at higher risk for cardiogenic shock and requiring mechanical ventilation, tracheostomy, and percutaneous endoscopic gastrostomy placement. Patients with a VA were also at lower risk for device thrombosis. Conversely, the VA group was at no higher risk for stroke. In comparing trends from 2002 to 2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased during this same period.In this retrospective study of the NIS database, VAs were common (45.4%) during the LVAD implantation admission. However, the occurrence of VAs during the implantation admission did not alter in-hospital mortality. More longitudinal studies are required to assess the long-term impact of VAs on mortality. In comparing trends from 2002-2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased.

Previous studies have reported the presence of subtle abnormalities in the right ventricular outflow tract (RVOT) in patients with apparently normal hearts and ventricular arrhythmias (VAs) from the RVOT, including the presence of low voltage areas (LVAs). This LVAs seem to be associated with the presence of ST-segment elevation in V1 or V2 leads at the level of the 2nd intercostal space (ICS).Our aim was to validate an electrocardiographic marker of LVAs in the RVOT in patients with idiopathic outflow tract VAs.A total of 120 patients were studied, 84 patients referred for ablation of idiopathic VAs with an inferior axis by the same operator, and a control group of 36 patients without VAs. Structural heart disease including arrhythmogenic right ventricular cardiomyopathy was ruled out in all patients. An electrocardiogram was performed with V1-V2 at the 2nd ICS, and ST-segment elevation ≥1 mm and T-wave inversion beyond V1 were assessed. Bipolar voltage map of the RVOT was performed in sinus rhythm (0.5-1.5 mV color display). Areas with electrograms1.5 mV were considered LVAs, and their presence was assessed. We compared three groups, VAs from the RVOT (n = 66), VAs from the LVOT (n = 18) and Control group (n = 36). ST-elevation, T-wave inversion and left versus right side of the VAs were tested as predictors of LVAs, respective odds ratio (ORs) (95% confidence interval [CI]) and p values, were calculated with univariate logist regression. Variables with a p .005 were included in the multivariate analysis.ST-segment elevation, T-wave inversion and LVAs were present in the RVOT group, LVOT group and Control group as follows: (62%, 17%, and 6%, p .0001), (33%, 29%, and 0%, p = .001) and (62%, 25%, and 14%, p .0001). The ST-segment elevation, T-wave inversion and right-sided VAs were all predictors of LVAs, respective unadjusted ORs (95% CI), p values were, 32.31 (11.33-92.13), p .0001, 4.137 (1.615-10.60), p = .003 and 8.200 (3.309-20.32), p .0001. After adjustment, the only independent predictor of LVAs was the ST-segment elevation, with an adjusted OR (95% CI) of 20.94 (6.787-64.61), p .0001.LVAs were frequently present in patients with idiopathic VAs. ST-segment elevation was the only independent predictor of their presence.

Tachycardia is characterized by high beating rates that can lead to life-threatening fibrillations. Mutations in several ion-channel genes were implicated with tachycardia; however, the complex genetic contributors and their modes of action are still unclear. Here, we investigated the influence of an SCN5A gene variant on tachycardia phenotype by deriving patient-specific iPSCs and cardiomyocytes (iPSC-CM). Two tachycardia patients were genetically analyzed and revealed to inherit a heterozygous p.F1465L variant in the SCN5A gene. Gene expression and immunocytochemical analysis in iPSC-CMs generated from patients did not show any significant changes in mRNA levels of SCN5A or gross NaV1.5 cellular mislocalization, compared to healthy-derived iPSC-CMs. Electrophysiological and contraction imaging analysis in patient iPSC-CMs revealed intermittent fibrillation-like states, occasional arrhythmic events, and sustained high-paced contractions that could be selectively reduced by flecainide treatment. The patch-clamp analysis demonstrated a negative shift in the voltage-dependent activation at the patient-derived iPSC-CMs compared to the healthy control line, suggestive of a gain-of-function activity associated with the SCN5A(+/p.F1465L) variant. Our patient-derived iPSC-CM model recapitulated the clinically relevant characteristics of tachycardia associated with a novel pathogenic SCN5A(+/p.F1465L) variant leading to altered Na+ channel kinetics as the likely mechanism underlying high excitability and tachycardia phenotype.

Mitral valve surgery employing a superior transseptal approach (STA) is associated with arrhythmogenicity and intra-atrial conduction delay, despite being optimal for visualization of the surgical field. It is sometimes difficult to treat atrial tachycardias (AT) that arise after STA. To investigate AT circuits that arise after STA in detail in order to identify the optimal ablation line, using ultra-high-resolution mapping (UHRM).We retrospectively analyzed 12 AT from 10 patients (median age 70 years, nine males) who had undergone STA surgery. The tachycardias were mapped using the Rhythmia mapping system (Boston Scientific, Natick, Massachusetts).The 12 STA-related AT (STA-AT) circuits were classifiable as follows according to location of the optimal ablation line: (1) peri-septal incision STA-AT (n = 3), (2) cavotricuspid isthmus (CTI) dependent STA-AT (n = 7), and (3) biatrial tachycardia (n = 2). Radiofrequency (RF) application terminated 11 of the 12 STA-AT. We found that difference in STA-AT circuit type was due to characteristics of the septal incision line made for STA. UHRM was important in identifying optimal ablation sites that did not create additional conduction disturbances in the right atrium (RA).ATs after STA involve complex arrhythmia circuits due to multiple and long incision lines in the RA. Accurate understanding of the arrhythmia circuit and sinus conduction in the RA after STA is recommended for treating post-surgical tachycardia in a minimally invasive manner.

Cardiac implantable electronic devices (CIEDs) store information continuously; however, the log of these devices is rarely analyzed in forensic practice. We retrospectively reviewed all cases referred for CIED interrogation by the Los Angeles County Department of Medical Examiner-Coroner between 2001 and 2020. According to the Department's practice, CIED interrogation may be requested for decedents in which details or cause of death are not clear from autopsy and clinical history. The CIED analysis was considered informative for the coroner's investigation either if it detected an arrhythmia or malfunction likely related to decedent's terminal event or if it was essential to determine time of death or identity of decedent. A total of 57 CIEDs were evaluated during the 20-year period. In almost half of cases (26/57: 45.6%), device analysis was informative for coroner's investigation. Arrhythmias likely related to terminal event were commonly detected (21/57: 36.8%). Device malfunction was identified as the likely cause of death in almost 10% of decedents (5/57: 8.8%), including three cases of battery depletion (3/57: 5.3%), one case of misclassification of ventricular tachycardia as supraventricular tachycardia with failure to deliver therapy (1/57: 1.7%), and one case of lead failure due to a broken pacing wire (1/57: 1.7%). Not infrequently, CIED interrogation was essential for determination of time of death (9/57: 15.8%), and there was one case (1/57: 1.7%) in which interrogation was essential for identifying the decedent. Our study shows that postmortem CIED interrogation can provide unique information regarding mechanism and time of death, and decedent's identity.

Before advancing to clinical trials, new drugs are screened for their pro-arrhythmic potential using a method that is overly conservative and provides limited mechanistic insight. The shortcomings of this approach can lead to the mis-classification of beneficial drugs as pro-arrhythmic.An in silico-in vitro pipeline was developed to circumvent these shortcomings. A computational human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model was used as part of a genetic algorithm to design experiments, specifically electrophysiological voltage clamp (VC) protocols, to identify which of several cardiac ion channels were blocked during in vitro drug studies. Such VC data, along with dynamically clamped action potentials (AP), were acquired from iPSC-CMs before and after treatment with a control solution or a low- (verapamil), intermediate- (cisapride or quinine) or high-risk (quinidine) drug.Significant AP prolongation (a pro-arrhythmia marker) was seen in response to quinidine and quinine. The VC protocol identified block of IWe developed an in silico-in vitro pipeline that simultaneously identifies pro-arrhythmia risk and mechanism of ion channel-blocking drugs. The approach offers a new tool for evaluating cardiotoxicity during preclinical drug screening.

This study was aimed to investigate the efficacy of the over-the-wire (OTW) microelectrodes catheter in coronary venous system (CVS) mapping and treatment of outflow tract ventricular arrhythmia (OTVA) arising from the vicinity of the left ventricular summit (LVS).Consecutive 62 patients with idiopathic OTVA in whom the OTW microelectrodes catheter was routinely used for CVS mapping were analyzed. CVS mapping was performed for both main trunk (from great cardiac vein to anterior interventricular vein) and branches including the annular branch or septal branch.The earliest activation site (EAS) was within the CVS in 21 patients. Among them, the EAS was within the main trunk of the CVS in seven (33%) and within the branch of the CVS in 14 (67%) patients. Radiofrequency catheter ablation was started at an anatomically adjacent site to the EAS, which eliminated OTVA in 16 (76%) patients (the endocardial LVOT in 10 and the aortic sinus of Valsalva in six patients). For the remaining five patients with unsuccessful catheter ablation at an anatomically adjacent site, targeted OTVA was eliminated by catheter ablation at the EAS within the CVS in two patients and by chemical ablation with ethanol injection in one patient, resulting in the overall success rate of 90% (19/21).The OTW microelectrodes-guided ablation of OTVA from the vicinity of the LVS was effective. In maximizing the efficacy of ablation, CVS branch mapping is important since the earliest activation was commonly recorded not in the main trunk but within the branch of the CVS.

We report a 28-year-old female patient with congenital type 2 long QT syndrome (LQTS) in which mexiletine shortened corrected QT interval (QTc) and effectively prevented refractory Torsade de Pointes (TdP) and ventricular fibrillation (VF). She developed TdP and VF, and was subsequently diagnosed with congenital type 2 LQTS. She had refractory TdP and VF every day despite medical therapy including β-blocker. They were completely suppressed after the initiation of mexiletine with shorting of QTc interval.

Epidemiological studies have suggested a lower incidence of arrhythmia-induced sudden cardiac death in women than in men. 17β-oestradiol (E2) has been reported to have a post-myocardial infarction antiarrhythmic effect, although the mechanisms have yet to be elucidated. We investigated whether E2-mediated antioxidation regulates macrophage polarization and affects cardiac sympathetic reinnervation in rats after MI. Ovariectomized Wistar rats were randomly assigned to placebo pellets, E2 treatment, or E2 treatment +3-morpholinosydnonimine (a peroxynitrite generator) and followed for 4 weeks. The infarct sizes were similar among the infarcted groups. At Day 3 after infarction, post-infarction was associated with increased superoxide levels, which were inhibited by administering E2. E2 significantly increased myocardial IL-10 levels and the percentage of regulatory M2 macrophages compared with the ovariectomized infarcted alone group as assessed by immunohistochemical staining, Western blot and RT-PCR. Nerve growth factor colocalized with both M1 and M2 macrophages at the magnitude significantly higher in M1 compared with M2. At Day 28 after infarction, E2 was associated with attenuated myocardial norepinephrine levels and sympathetic hyperinnervation. These effects of E2 were functionally translated in inhibiting fatal arrhythmias. The beneficial effect of E2 on macrophage polarization and sympathetic hyperinnervation was abolished by 3-morpholinosydnonimine. Our results indicated that E2 polarized macrophages into the M2 phenotype by inhibiting the superoxide pathway, leading to attenuated nerve growth factor-induced sympathetic hyperinnervation after myocardial infarction.

INTRODUCTION mitral valve prolapse(MVP) is a common disease in women, causing chest pain and palpitation, due to structural and functional valve abnormality, sometime associated with gastro-esophageal-reflux-disease(GERD).This is a challenging clinical problem in clinical practice,requires targeted diagnostic assessment,to identify the underlying causes of the symptoms because treatment needs to be tailored,according to the causes themselves, to resolve the symptoms. Our aim is to assess the prevalence of GERD in a population of postmenopausal women affected by MVP and if there is any correlation between the two conditions. PATIENTS AND METHODS MVP diagnosis was performed by echocardiograpic examination,according to ASE(American-Society-Echocardiography) criteria. 289 consecutive MVP women,symptomatic for chest pain and palpitation,were included,250 consecutive women without MVP, symptomatic for chest pain and palpitation were control group(CG).GERD diagnosis was performed according to 2013 ACG(American-College-Gastroenterology) criteria,women affected by thyroid disorders, all heart disease, including mitral disease with moderate or severe mitral regurgitation,gastrointestinal diseases assessed by gastroscopy were excluded. RESULTS 31(11%) women were affected by GERD,among 289 with MVP, 11(4.4%) women were affected by GERD,among 250 on CG,Chi-squared 8.1,Odds ratio 2.7,c.i.95%,p

The two most common postoperative atrial flutter (AFL) circuits after right atriotomy are the cavotricuspid isthmus (CTI) dependent and the lateral, peri-incisional. We investigated whether radiofrequency ablation (RFA) of both circuits results in more favorable long-term outcomes.Single-center retrospective cohort study of consecutive patients who underwent RFA of AFL after open-heart surgery. The effect of surgery type and RFA strategy on AFL recurrence was evaluated.One hundred and forty-two patients (mean age 64.5 ± 12.7 years, 65.% male) were enrolled. Patients with right atrial (RA) flutter (n = 124) were divided into two groups based on the index RFA procedure: only one RA circuit was ablated (Group 1, n = 84, 67.7%) or both the CTI and the peri-incisional circuit ablated (Group 2, n = 40, 32.3%). The previous open-heart surgery was categorized based on the extension of the RA incision: limited (Type A) or extended (Type B) atriotomy. After a mean follow-up of 36 ± 28 months, flutter recurrence was not different among patients with limited RA atriotomy (25% vs. 22% in Groups 1A and 2A, respectively, p = 1.0). However, after type B surgery, ablation of both AFL circuits was associated with a reduced recurrence rate (63% vs. 26% in Groups 1B and 2B, respectively, p = .002).In patients with postoperative RA flutter after extended right atriotomy, ablation of both the CTI and the peri-incisional isthmus significantly reduces the AFL recurrence rate. Prophylactic ablation of both isthmi, even if not proven to support reentry, is reasonable in this population.

When combined with nalbuphine, local anesthetics show a longer duration of nerve block without increasing complications. However, no evidence is available concerning the effect of nalbuphine on the cardiotoxicity of local anesthetics. The objective of this work is to investigate whether nalbuphine pretreatment can increase the lethal dose threshold of ropivacaine in rats. Anesthetized Sprague Dawley rats were pretreated with different doses of nalbuphine (0.4, 0.8, 1.5, 3.0, 5.0 mg/kg) or NS (normal saline, negative control) or 30% LE (lipid emulsion, positive control) 2 ml/kg/min for 5 min (n = 6). Then 0.5% ropivacaine was infused at a rate of 2.5 mg/kg/min until asystole occurs. Time of arrhythmia, 50% mean arterial pressure- and 50% heart rate-reduction, and asystole were recorded, and ropivacaine doses were calculated. Nalbuphine (0.4-5.0 mg/kg) did not affect ropivacaine-induced arrhythmia, 50% mean arterial pressure-reduction and 50% heart rate-reduction, and asystole in rats compared with NS pre-treatment. The asystole dose threshold (in milligrams per kilogram) of group LE was higher than that of group NS (NS 28.25(6.32) vs. LE, 41.58(10.65); P = 0.04; 95% confidence interval 0.23 to 26.45), while thresholds of arrhythmia, 50% mean arterial pressure-reduction, and 50% heart rate-reduction were not affected by LE. Nalbuphine doses of 0.4-5.0 mg/kg pretreatment did not increase the threshold of ropivacaine cardiotoxicity compared with NS control; 30% LE increases the lethal dose threshold of ropivacaine in rats.

Previous studies have suggested an association between sulfonylureas and an increased risk of cardiovascular death among patients with type 2 diabetes. A potential mechanism involves sulfonylurea-induced ventricular arrhythmias (VAs). We conducted a systematic review of observational studies to determine whether the use of sulfonylureas, compared with the use of other antihyperglycemic drugs, is associated with the risk of VA (ventricular tachycardia, ventricular fibrillation, and premature ventricular complexes), cardiac arrest, and sudden cardiac death among patients with type 2 diabetes. Two independent reviewers searched MEDLINE, EMBASE, CINAHL Plus, CENTRAL, and ClinicalTrials.gov from inception to July 2021 for observational studies comparing sulfonylureas vs. other antihyperglycemic therapies or intraclass comparisons of sulfonylureas. Our systematic review included 17 studies (1,607,612 patients). Per Risk Of Bias In Non-randomized Studies of Interventions (ROBINS)-I, there were few high-quality studies (2 studies at moderate risk of bias; 4 at serious risk; and 11 at critical risk). All studies at a moderate or serious risk of bias reporting comparisons with other therapies were consistent with an increased risk of VA. Sulfonylureas were associated with a higher risk of arrhythmia vs. dipeptidyl peptidase-4 inhibitors (adjusted hazard ratio (aHR): 1.52, 95% confidence interval (CI): 1.27-1.80) and of VA vs. metformin (aHR: 1.52, 95% CI: 1.10-2.13). One moderate quality study reported inconsistent results for a composite of cardiac arrest/VA in analyses of US Medicaid claims and Optum claims data. Our systematic review suggests that, among higher-quality observational studies, sulfonylureas are associated with an increased risk of VA. However, we identified few methodologically rigorous studies, underscoring the need for additional real-world studies.

Background: Ventricular arrhythmias (VAs) are observed in 25-50% of continuous-flow left ventricular assist devices (CF-LVAD) recipients, but their role on mortality is debated. Methods: Sixty-nine consecutive patients with a CF-LVAD were retrospectively analyzed. Study endpoints were death and occurrence of first episode of VAs post-CF-LVAD implantation. Early VAs were defined as VAs in the first month after CF-LVAD implantation. Results: During a median follow-up of 29.0 months, 19 patients (27.5 %) died and 18 patients (26.1%) experienced VAs. Three patients experienced early VAs, and one of them died. Patients with cardiac resynchronization therapy (CRT-D) showed a trend towards more VAs (p=0.076), compared to patients without CRT-D; no significant difference in mortality was found between patients with and without CRT-D (p=0.63). Patients with biventricular (BiV) pacing ≥98% experienced more frequently a VAs (p=0.046), with no difference in mortality (p=0.56), compared with patients experiencing BiV pacing

Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVAD) improve outcomes in heart failure patients. Early ventricular arrhythmias (VA) are common after LVAD and are associated with increased mortality. The association between left ventricular pacing (LVP) with CRT and VAs in the early post-LVAD period remains unclear.This was a retrospective study of all patients undergoing LVAD implantation from 1/2016 to 12/2019. Patients were divided into those with CRT and active LVP (CRT-LVP) immediately post-LVAD implant versus those without CRT-LVP. Implantable cardiac defibrillator electrograms were reviewed and early VAs were defined as sustained ventricular tachycardia (VT)/ventricular fibrillation occurring within 30 days of LVAD implantation.Of 186 included patients (mean age 53 years, 75% male, mean body mass index 28), 72 had CRT devices, 63 of whom had LV pacing enabled after LVAD implant (CRT-LVP group). Patients with CRT-LVP were more likely to have VA in the early postoperative period (21% vs. 4%; p = .0001). All 9 patients with CRT in whom LVP was disabled had no early VA. Among those with early VA, patients with CRT-LVP were more likely to have monomorphic VT (77% vs. 40%; p = .07). In multiple logistic regression, CRT-LVP pacing remained an independent predictor of early VA after adjustment for history of VA and AF.Patients with CRT-LVP after LVAD implant had a higher incidence of early VA (specifically monomorphic VT). Epicardial LV pacing may be proarrhythmic in the early postoperative period after LVAD.

Focal ventricular arrhythmias (VAs) originating from the intramural myocardium of the basal septum are difficult to localize and ablate. Proximal septal veins emptying into the great cardiac vein can reach close to the origin of intramural arrhythmias.To assess characteristics of proximal septal coronary veins in patients with intramural VAs.Among 84 consecutive patients with intramural VAs, 29 patients (age 60 ± 11years, 16 males, ejection fraction 47 ± 13%) underwent preprocedural cardiac computed tomographic angiography (CTA). In 14 of these patients, the intramural site of origin (SOO) was identified with multipolar catheters. The intramural SOO could not be accessed with mapping catheters in the other 15 patients while mapping the coronary venous system. The CTA identified sizable proximal septal veins in all patients in whom the SOO could be accessed with mapping catheters. In the patients in whom the intramural SOO was not identified, the proximal septal veins were often either small (2 mm at the branching site) or non-existent (n = 9, p = .001). The proximal septal veins in patients in whom the SOO was identified were larger than in the patients in whom the SOO could not be identified (3.0 ± 0.6 mm vs. 2.1 ± 0.9 mm, p = .01).Preprocedural imaging with CTAs can be beneficial in identifying the anatomy of proximal septal coronary veins that allow adequate mapping of patients with suspected intramural VAs.

A wearable cardioverter defibrillator (WCD) is indicated in appropriate patients to reduce the risk for sudden cardiac death. Challenges for patients wearing a WCD have been frequent false shock alarms primarily due to electrocardiogram noise and wear discomfort. The objective of this study was to test a contemporary WCD designed for reduced false shock alarms and improved comfort.One hundred and thirty patients with left ventricular ejection fraction ≤40% and an active implantable cardioverter defibrillator (ICD) were fitted with the ASSURE WCD (Kestra Medical Technologies) and followed for 30 days. WCD detection was enabled and shock alarm markers recorded, but shocks and shock alarms were disabled. All WCD episodes and ICD ventricular tachycardia/ventricular fibrillation (VT/VF) episodes were adjudicated. The primary endpoint was the false-positive shock alarm rate with a performance goal of 1 every 3.4 days (0.29 per patient-day).Of 163 WCD episodes, 4 were VT/VF and 159 non-VT/VF (121 rhythms with noise, 32 uncertain with noise, 6 atrial flutter without noise). Only three false-positive shock alarm markers were recorded; one false-positive shock alarm every 1333 patient-days (0.00075 per patient-day, 95% confidence interval: 0.00015-0.00361; p .001). No ICD recorded VT/VF episodes meeting WCD detection criteria (≥170 bpm for ≥20 s) were missed by the WCD during 3501 patient-days of use. Median wear was 31.0 days (interquartile range [IQR] 2.0) and median daily use 23.0 h (IQR 1.7). Adverse events were mostly mild: skin irritation (19.4%) and musculoskeletal discomfort (8.5%).The ASSURE WCD demonstrated a low false-positive shock alarm rate, low patient-reported discomfort, and no serious adverse events.

Develop a deflectable intracardiac MR imaging (ICMRI) guiding-sheath to accelerate imaging during MR-guided electrophysiological (EP) interventions for radiofrequency (500 kHz) ablation (RFA) of arrythmia. Requirements include imaging at three to five times surface-coil SNR in cardiac chambers, vascular insertion, steerable-active-navigation into cardiac chambers, operation with ablation catheters, and safe levels of MR-induced heating.ICMRI's 6 mm outer-diameter (OD) metallic-braided shaft had a 2.6 mm OD internal lumen for ablation-catheter insertion. Miniature-Baluns (MBaluns) on ICMRI's 1 m shaft reduced body-coil-induced heating. Distal section was a folded "star"-shaped imaging-coil mounted on an expandable frame, with an integrated miniature low-noise-amplifier overcoming cable losses. A handle-activated movable-shaft expanded imaging-coil to 35 mm OD for imaging within cardiac-chambers. Four MR-tracking micro-coils enabled navigation and motion-compensation, assuming a tetrahedron-shape when expanded. A second handle-lever enabled distal-tip deflection. ICMRI with a protruding deflectable EP catheter were used for MR-tracked navigation and RFA using a dedicated 3D-slicer user-interface. ICMRI was tested at 3T and 1.5T in swine to evaluate (a) heating, (b) cardiac-chamber access, (c) imaging field-of-view and SNR, and (d) intraprocedural RFA lesion monitoring.The 3T and 1.5T imaging SNR demonstrated400% SNR boost over a 4 × 4 × 4 cmICMRI assisted EP-catheter navigation to difficult targets and accelerated RFA monitoring.

Heart failure with recovered ejection fraction (HFrecEF) involves those who have previously had reduced cardiac function that has subsequently improved. However, there is not a single definition of this phenomenon and recovery of cardiac function in terms of left ventricular ejection fraction (LVEF) itself does not necessarily correlate with remission from the detrimental physiology of heart failure (HF) and its consequences. There is also the question of the utility of defibrillators in these patients, and whether they should be replaced at the time of battery depletion. To address this, several studies have shown specific predictors of ensuing LVEF recovery, including patient demographics, co‐morbidities, and medication use, as well as predictors of ventricular arrhythmias (VA) following LVEF recovery. Recent studies have also shown novel imaging parameters that may aid in predicting which patients would have a higher risk of these arrhythmias. Additional data describe a small, yet appreciable risk of VA, in addition to appropriate shocks as well. In this review, we describe predictors of LVEF recovery, carefully analyse and characterize the continued risk for VA and appropriate shocks following LVEF recovery, and explore additional novel modalities that may aid in decision‐making.

J wave syndrome is a spectrum of proarrhythmic disorders including Brugada syndrome and early repolarization syndrome (ERS), that are prone to ventricular fibrillation and sudden cardiac death (SCD). In this case report we present a patient with ERS and aborted SCD complicated with cognitive impairment. We also investigated whether performing transcranial direct current stimulation to target his cognitive impairment, interfered with the function of his implantable cardioverter defibrillator.

Background: Myocarditis have variable clinical presentation, evolution and prognosis. Aim of our study was to evaluate the value of speckle tracking echocardiography and cardiac magnetic resonance (CMR) in the short-term prediction of supraventricular arrhythmias (SVA) in patients with acute myocarditis. Methods: Seventy patients (mean age 31±14 years old) with acute myocarditis and preserved left ventricular ejection fraction (LVEF) were enrolled. Longitudinal systolic strain (LS) of the left ventricle (LV), mechanical dispersion (MD) and CMR with quantitative measurement of delayed enhancement (DE) were performed in a subset of 43 patients. Logistic regression and ROC analysis were used to identify predictors of SVA. Results: Only LS measured at sup-epicardial, mid-wall and sub-endocardial level of the apical 4-chamber view was significantly lower in patients with SVA, while MD was marginally prolonged in this setting. A value of LS>- 16.1% measured at LV mid-wall in the apical 4-chamber view (ROC-AUC.75, Sensitivity 63%, Specificity 85%) was the most accurate measure to identify patients with SVA. DE mass was also helpful with a ROC-AUC.76; a DE-Mass>18.9 gr. had a Sensitivity 63% and a Specificity 77%, to identify patients at risk of SVA. Conclusions: Both DE mass and LS were associated with higher risk of SVA in patients with acute myocarditis and preserved LVEF. However, LS measured at the mid-wall level and limited to LV segments included in the apical 4-chamber view was the most accurate measure and did not show interaction with DE mass.

Artificial oxygen carriers (HbV) can treat hemorrhagic shock with lethal arrhythmias (VT/VF). No reports exist on subacute HbV's effects.Acute and subacute resuscitation effects with anti-arrhythmogenesis of HbV were studied in 85% blood exchange rat model (85%-Model). Lethal 85%-Model was created by bone marrow transfusion and femoral artery bleeding in 80 SD rats in HbV-administered group (HbV-group), washed erythrocyte-administered group (wRBC-group), and 5% albumin-administered group (ALB-group). Survival rates, anti-arrhythmic efficacy by optical mapping system (OMP) with electrophysiological study (EPS) in Langendorff heart, cardiac autonomic activity by heart rate variability (HRV) and ventricular arrhythmias by 24-h electrocardiogram telemetry monitoring (24 h-ECG) in awake, and left ventricular function by echocardiography (left ventricular ejection fraction [LVEF]) were measured.All rats in HbV- and wRBC-groups survived for 4 weeks, whereas no rats in ALB-group. HbV and wRBC acutely suppressed VT/VF in Langendorff heart through ameliorating action potential duration dispersion (APDd) analyzed by OMP with EPS. For subacute analysis, 50% blood exchange by 5% albumin was used (ALB-group 50). Subacute salutary effect on APDd and VT/VF inducibility was confirmed in HbV- and wRBC-groups. 24 h-ECG showed that HbV and wRBC suppressed none-sustained ventricular tachycardia (NSVT) and sympathetic component of HRV (LF/HF) with preserved LVEF (HbV-group, wRBC-group vs. ALB-group 50; NSVT numbers/days, 0.5 ± 0.3, 0.4 ± 0.3 vs. 3.9 ± 1.2*; LF/HF, 1.1 ± 0.2, 0.8 ± 0.2 vs. 3.5 ± 1.0*; LVEF, 84 ± 5, 83 ± 4, vs. 77 ± 4%*; *p 0.05).Collectively, HbV has sustained antiarrhythmic effect in subacute 85%-Model by ameliorating electrical remodeling and improving arrhythmogenic modifying factors (HRV and LVEF). These findings are useful in now continuing clinical trials of HbV.

Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias.Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020).Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.

Numerous reports of neuropsychiatric symptoms highlighted the pathologic potential of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its relationship the onset and/or exacerbation of mental disease. However, coronavirus disease 2019 (COVID‐19) treatments, themselves, must be considered as potential catalysts for new‐onset neuropsychiatric symptoms in COVID‐19 patients. To date, immediate and long‐term neuropsychiatric complications following SARS‐CoV‐2 infection are currently unknown. Here we report on five patients with SARS‐CoV‐2 infection with possible associated neuropsychiatric involvement, following them clinically until resolution of their symptoms. We will also discuss the contributory roles of chloroquine and dexamethasone in these neuropsychiatric presentations., Highlights SARS‐CoV‐2 Infection and COVID‐19 treatments have a potential catalytic role on neuropsychiatric complications.Cytokine storm and exacerbated cytotoxicity could be implicated in COVID‐19 related neuropsychiatric symptoms.The use of corticosteroids must be considered balancing risk/benefit to the patient.

Inherited arrhythmia conditions (IAC) can lead to sudden cardiac death at any age, and relatives of an affected person have up to a 50% chance of inheriting the condition and are at risk for developing features. Cascade testing is a stepwise approach for identifying relatives at risk for IACs through clinical screening and genetic testing. Early detection can reduce morbidity and mortality for affected individuals and determine potential risk mitigation strategies for relatives. However, cardiovascular genetic studies have reported an incomplete uptake of cascade testing in at-risk relatives. We explored patient perspectives on cascade testing for IACs and alternative approaches to family communication. Twelve semi-structured phone interviews were conducted with probands of the British Columbia Inherited Arrhythmia Program confirmed to carry a pathogenic or likely pathogenic variant in a gene associated with an IAC. Thematic analysis of transcripts through an iterative coding process revealed five main themes: (a) a stepwise approach is followed in disclosing risk to relatives, (b) relatives' autonomy in cascade testing is supported, (c) lived experience with the condition influences disclosure and uptake of cascade testing, (d) collaborative approach to informing relatives reduces negative impact of disclosure, and (e) direct contact from a healthcare provider is viewed as acceptable. The findings highlight this patient cohort's experiences and opinions with approaches to disclosure and demonstrate their understanding and acceptance of their relatives' approaches to cascade testing. In addition, while the notion of direct contact was generally accepted, a collaborative approach to contacting relatives between the proband and provider may be most effective.

To determine the common clinical signs, with onset and duration, treatments given, and outcome in dogs with acute, accidental exposure to salbutamol.Retrospective study.Five hundred and one canine cases reported to the UK's Veterinary Poisons Information Service (VPIS).A review of all records in the VPIS database for dogs exposed to salbutamol was carried out. After applying inclusion and exclusion criteria, the records of 501 dogs were further analyzed. The most common clinical signs were tachycardia (80.6%), tachypnea (32.9%), depression (21.0%), and vomiting (19.2%). The dose was unknown in most cases as the dogs typically pierced a salbutamol inhaler. The blood potassium concentration was measured in at least 142 dogs and hypokalemia was reported in 21.2% (106/501), 18 (17%) of which had associated weakness, twitching, or collapse. Three dogs had paralysis probably as a result of hypokalemia, although no potassium concentration was reported in these cases. Arrhythmias occurred in 17 dogs (3.4%), and 7 required pharmacological intervention. There were no reports of persistent cardiac injury or thermal injury from the compressed gas present in some salbutamol products. Signs were rapid in onset, generally within 1-3 h, and, where time to outcome was recorded (n = 172), 78% of dogs recovered within 24 h. Of the 501 dogs, no treatment was required in 27.9%. Beta-blockers were used in 39.5%, intravenous fluids in 28.7%, and potassium supplementation in 15.8%. Overall, 30 dogs remained asymptomatic (6.0%), 469 recovered (93.6%), and 2 dogs (0.4%) died.Most dogs exposed to salbutamol rapidly develop clinical signs; these were commonly increased heart and respiration rates. Hypokalemia and arrhythmias (particularly ventricular arrhythmias) are potential complications. Any dog that chews a salbutamol inhaler should be assessed promptly for signs of toxicosis. Prognosis in dogs with acute salbutamol exposure is good, but more guarded in those with severe tachycardia and at risk of cardiac injury.

Ethanol ablation (EA) is an alternative option for subjects with ventricular arrhythmias (VAs) refractory to conventional medical and ablative treatment. However, data on the efficacy and safety of EA remain sparse.A systematic literature search was conducted. The primary outcomes were 1) freedom from the targeted VA and 2) freedom from any VAs post-EA. Additional safety outcomes were also analyzed.Ten studies were selected accounting for a population of 174 patients (62.3 ± 12.5 years, 94% male) undergoing 185 procedures. The overall acute success rate of EA was 72.4% (confidence interval [CIEA is a valuable therapeutic option for VAs refractory to conventional treatment and can result in 1-year freedom from VA recurrence in 60%-75% of the patients. However, anatomical or technical challenges preclude acute success in almost 30% of the candidates and the rate of complication is not insignificant, highlighting the importance of well-informed patient selection. The certainty of the evidence is low, and further research is necessary.

Background Coronavirus disease‐2019 (COVID‐19) has been associated with an increased risk of acute cardiac events. However, the effect of COVID‐19 on repolarization heterogeneity is not yet established. In this study, we evaluated electrocardiogram (ECG) markers of repolarization heterogeneity in patients hospitalized with COVID‐19. In addition, we performed a systematic review and meta‐analysis of the published studies. Methods QT dispersion (QTd), the interval between T wave peak to T wave end (TpTe), TpTe/QT (with and without correction), QRS width, and the index of cardio‐electrophysiological balance (iCEB) were calculated in 101 hospitalized COVID‐19 patients and it was compared with 101 non‐COVID‐19 matched controls. A systematic review was performed in four databases and meta‐analysis was conducted using Stata software. Results Tp‐Te, TpTe/QT, QRS width, and iCEB were significantly increased in COVID‐19 patients compared with controls (TpTe = 82.89 vs. 75.33 ms (ms), p‐value = .005; TpTe/QT = 0.217 vs. 0.203 ms, p‐value = .026). After a meta‐analysis of 679 COVID‐19 cases and 526 controls from 9 studies, TpTe interval, TpTe/QT, and TpTe/QTc ratios were significantly increased in COVID‐19 patients. Meta‐regression analysis moderated by age, gender, diabetes mellitus, hypertension, and smoking reduced the heterogeneity. QTd showed no significant correlation with COVID‐19. Conclusion COVID‐19 adversely influences the ECG markers of transmural heterogeneity of repolarization. Studies evaluating the predictive value of these ECG markers are warranted to determine their clinical utility.

To test whether a high defibrillation threshold (DFT) marks patients with poor outcomes which are improved when DFT is decreased by system modification (subcutaneous coil implant; SM).The electrical substrate generating fast ventricular arrhythmias may generate poor outcomes among patients treated with implantable cardioverter-defibrillators (ICDs), even when arrhythmias are treated successfully. Since patients with high DFTs have increased mortality, we contrasted survival among patients with high DFT treated with and without SM.We studied consecutive patients undergoing ICD implantation and DFT testing at Cleveland Clinic over a 14-year period. High DFT was defined as successful defibrillation by shock strength25 J or ≤10 J of maximal device output. Mortality was recorded using the Social Security Death Index. Survival was compared among those high DFT patients receiving SM versus the remainder.Out of 6353 patients tested, 191 (3%) had high DFT (32.1 ± 3.7 J) versus 13.9 ± 4.9 J in the remainder ("acceptable DFT," p .001). One hundred twenty-one high DFT patients (63%; 33.3 ± 3.4 J) underwent SM, which significantly decreased DFT (24.8 ± 5.9 J; p .001). Seventy patients (37%; 30.3 ± 3.3 J) did not undergo SM. During follow-up, 38% (2363/6162; 7.8 yrs) patients with acceptable DFT died versus 48% high DFT patients (91/191; 5.6 yrs.; p .001). Concomitantly, 48% patients with SM (58/121) died, as compared to 47% patients (33/70) without SM (p = .91); median follow-up 4.9 yrs).Patients with high DFT have a higher mortality than those with acceptable DFT. The additional subcutaneous coil implant decreases DFT to an acceptable range but does not appear to improve survival. The electrical substrate underlying high DFT appears to determine survival.

His-bundle pacing (HBP) and left-bundle-area pacing (LBAP) are conduction system pacing (CSP) modalities increasingly used as alternatives to conventional biventricular pacing (BiVP). While effects of CSP on ventricular depolarization have been reported, effects on ventricular repolarization have not.QRS duration (QRSd) and validated ECG parameters of ventricular repolarization associated with arrhythmic risk (T-peak-to-T-endAlthough QRSd was shorter with HBP versus LBAP (119 ± 7 ms vs. 132 ± 9 ms, p = .02), there were no significant differences in any repolarization parameters between these methods of CSP. However, when comparing CSP (HBP + LBAP) to BiVP, both QRSd (125 ± 5 ms vs. 147 ± 7 ms, p .0001) and repolarization parameters (T-peak-to-T-endIn addition to improved depolarization, CSP reduced repolarization heterogeneity and provided greater T-wave memory resolution as compared to BiVP. Both modalities of CSP (HBP + LBAP) resulted in comparably reduced repolarization heterogeneity regardless of baseline QRSd and LV function. These observations may confer lower arrhythmogenic risk and warrant further study.

Congenital long QT syndrome (LQTS) is a familial cardiac ion channelopathy first described over sixty years ago. It is characterised by prolonged ventricular repolarization (long QT on ECG), ventricular arrhythmias and associated syncope or sudden cardiac death. As the most closely studied cardiac channelopathy, over the decades we have gained a deep appreciation of the complex genetic model of LQTS. Variability in genetic expression and incomplete penetrance leads to a heterogenous phenotype that can be challenging to clinically classify. In recent times, progress has been made in diagnostic method, risk stratification and treatment options. This review has been written as a guide for the general cardiologist to understand the basic pathophysiology, diagnosis, and management priorities for the most encountered LQTS subtypes: LQT1, LQT2 and LQT3. This article is protected by copyright. All rights reserved.

Malaria remains the leading cause of parasitic death in the world. Artemisinin resistance is an emerging threat indicating an imminent need for novel combination therapy. Given the key role of mass drug administration, it is pivotal that the safety of anti-malarial drugs is investigated thoroughly prior to widespread use. Cardiotoxicity, most prominently arrhythmic risk, has been a concern for anti-malarial drugs. We clarify the likely underlying mechanisms by which anti-malarial drugs predispose to arrhythmias. These relate to disruption of (1) action potential upstroke due to effects on the sodium currents, (2) action potential repolarisation due to effects on the potassium currents, (3) cellular calcium homeostasis, (4) mitochondrial function and reactive oxygen species production and (5) cardiac fibrosis. Together, these alterations promote arrhythmic triggers and substrates. Understanding these mechanisms is essential to assess the safety of these drugs, stratify patients based on arrhythmic risk and guide future anti-malarial drug development.

The reduced density of cardiac autonomic nerves plays an important role in malignant arrhythmia after myocardial infarction (MI). Previous studies have shown that there is an interaction between the brain and the heart, and fastigial nucleus electrostimulation (FNS) promotes central nerve regeneration. Whether and how it can promote cardiac nerve regeneration after MI and the underlying mechanisms remain unknown. This study investigated whether FNS promotes cardiac nerve regeneration and reduces malignant arrhythmia inducibility in a post-infarction rat model. Ninety-eight Wistar rats were randomly assigned to Sham control, MI (left anterior descending coronary artery ligation without FNS), FNS (MI plus FNS), and FNL (fastigial nucleus lesion plus FNS plus MI) groups. The frequency of malignant arrhythmia was significantly lower in the FNS group than in the MI and FNL groups. The density of cardiac autonomic nerves was less in the MI group than in the Sham group, which was promoted by FNS. The nerve growth factor (NGF) mRNA expression was downregulated in the MI group compared to the Sham group, which was significantly enhanced by FNS. The expression levels of norepinephrine (NE) and acetylcholine (ACh) were higher and lower respectively in the MI and FNL groups than in the Sham group. After FNS, NE concentration was reduced and Ach level was elevated compared to the MI group. These data suggested that FNS promoted the regeneration of cardiac autonomic nerves and reduced the incidence of malignant arrhythmias in MI rat model. The mechanisms might involve up-regulation of NGF mRNA expression, decrease of NE release and increase of ACh release.

BACKGROUND Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS AND RESULTS Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 μM), indomethacin (Group 2, n = 13; 10 and 20 μM) and diclofenac (Group 3, n = 13; 10 and 20 μM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations. CONCLUSION The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.

Despite advances in drug and catheter ablation therapy, long-term recurrence rates for ventricular tachycardia remain suboptimal. Cardiac stereotactic body radiotherapy (SBRT) is a novel treatment that has demonstrated reduction of arrhythmia episodes and favorable short-term safety profile in treatment-refractory patients. Nevertheless, the current clinical experience is early and limited. Recent studies have highlighted variable duration of treatment effect and substantial recurrence rates several months postradiation. Contributing to these differential outcomes are disparate approaches groups have taken in planning and delivering radiation, owing to both technical and knowledge gaps limiting optimization and standardization of cardiac SBRT.In this report, we review the historical basis for cardiac SBRT and existing clinical data. We then elucidate the current technical gaps in cardiac radioablation, incorporating the current clinical experience, and summarize the ongoing and needed efforts to resolve them.Cardiac SBRT is an emerging therapy that holds promise for the treatment of ventricular tachycardia. Technical gaps remain, to be addressed by ongoing research and growing clincial experience.

Aims We tested the hypothesis that shortening of time‐to‐peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long‐term volumetric responders [end‐systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT). Methods Td was analysed in an animal study (n = 12) of left bundle‐branch block (LBBB) with extensive instrumentation to detect left ventricular myocardial deformation, electrical activation, and pressures during pacing. The sum of electrical delays from the onset of pacing to four intracardiac electrodes formed a synchronicity index (SI). Pacing was performed at baseline, with LBBB, right and left ventricular pacing and finally with biventricular pacing (BIVP). We then studied Td at baseline and with BIVP in a clinical observational study in 45 patients during the implantation of CRT and followed up for up to 88 months. Results We found a strong relationship between Td and SI in the animals (R = 0.84, P

Objective Cardiac alterations represent a potential epilepsy‐associated comorbidity. Whether cardiac changes occur as a function of epilepsy duration is not well understood. We sought to evaluate whether cardiac alterations represented a time‐dependent phenomenon in pediatric epilepsy. Methods We retrospectively followed pediatric epilepsy patients without preexisting cardiac conditions or ion channelopathies who had history of pediatric intensive care unit admission for convulsive seizures or status epilepticus between 4/2014 and 7/2017. All available 12‐lead electrocardiograms (ECGs) from these patients between 1/2006 and 5/2019 were included. We examined ECG studies for changes in rhythm; PR, QRS, or corrected QT intervals; QRS axis or morphology; ST segment; or T wave. Data were analyzed using multivariable models containing covariates associated with ECG changes or epilepsy duration from the univariate analyses. Results 127 children with 323 ECGs were included in the analyses. The median epilepsy duration was 3.9 years (IQR 1.3‐8.4 years) at the time of an ECG study and a median of 2 ECGs (IQR 1‐3) per subject. The clinical encounters associated with ECGs ranged from well‐child visits to status epilepticus. We observed changes in 171 ECGs (53%), with 83 children (65%) had at least 1 ECG with alterations. In a multivariable logistic regression model adjusting for potentially confounding variables and accounting for clustering by patient, epilepsy duration was independently associated with altered ECGs for each year of epilepsy (OR: 1.1, 95% CI: 1.0‐1.2, P = .002). Extrapolating from this model, children with epilepsy durations of 10 and 15 years had 2.9 and 4.9 times the odds of having ECG changes, respectively. Significance Cardiac alterations may become more common with increasing epilepsy duration in select pediatric epilepsy patients. Future studies are needed to determine the potential clinical implications and the generalizability of these observations.

BackgroundPregnant women with a substance-related diagnosis, such as an alcohol use disorder, are a vulnerable population that may experience higher rates of severe maternal morbidity, such as hemorrhage and eclampsia, than pregnant women with no substance-related diagnosis.MethodsThis retrospective cross-sectional study reviewed electronic health record data on women (aged 18-44years) who delivered a single live birth or stillbirth at ≥ 20weeks of gestation from March 1, 2016, to August 30, 2019. Women with and without a substance-related diagnosis were matched on key demographic characteristics, such as age, at a 1:1 ratio. Adjusting for these covariates, odds ratios and 95% confidence intervals were calculated.ResultsA total of 10,125 deliveries met the eligibility criteria for this study. In the matched cohort of 1,346 deliveries, 673 (50.0%) had a substance-related diagnosis, and 94 (7.0%) had severe maternal morbidity. The most common indicators in women with a substance-related diagnosis included hysterectomy (17.7%), eclampsia (15.8%), air and thrombotic embolism (11.1%), and conversion of cardiac rhythm (11.1%). Having a substance-related diagnosis was associated with severe maternal morbidity (adjusted odds ratio=1.81 [95% CI, 1.14-2.88], p-value=0.0126). In the independent matched cohorts by substance type, an alcohol-related diagnosis was significantly associated with severe maternal morbidity (adjusted odds ratio=3.07 [95% CI, 1.58-5.95], p-value=0.0009), while the patterns for stimulant- and nicotine-related diagnoses were not as well resolved with severe maternal morbidity and opioid- and cannabis-related diagnoses were not associated with severe maternal morbidity.ConclusionWe found that an alcohol-related diagnosis, although lowest in prevalence of the substance-related diagnoses, had the highest odds of severe maternal morbidity of any substance-related diagnosis assessed in this study. These findings reinforce the need to identify alcohol-related diagnoses in pregnant women early to minimize potential harm through intervention and treatment.