Intranasal etripamil for rapid treatment of paroxysmal supraventricular tachycardia.

Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia that, although usually benign, can occur unpredictably, cause disabling symptoms and significantly impair quality of life. If spontaneous resolution does not occur, the only current self-treatment is for the patient to attempt vagal maneuvers, however, these are frequently unsuccessful. Hospital attendance is then required for intravenous therapy. Etripamil, an intranasal calcium channel blocker similar to verapamil, may be able to fill this therapeutic gap, allowing rapid self-treatment of PSVT at home. This narrative review discusses the latest evidence for etripamil and its potential role in future clinical practice.

Paroxysmal supraventricular tachycardia (PSVT) is an abnormal heart rhythm, causing the heart to beat rapidly. There are several ways to treat PSVT. This article discusses a new therapy, etripamil. One treatment involves breathing techniques called 'vagal maneuvers'. These avoid medication and sometimes stop the abnormal rhythm, however, in many cases, this does not work. An alternative is a tablet taken when symptoms occur. Unfortunately, tablets take time to absorb, meaning symptoms may continue until the medication takes effect, and this approach does not work for everyone. If these approaches fail, patients suffering from PSVT may need to seek treatment at a hospital. This may involve intravenous therapy, with certain drugs causing unpleasant sensations of chest discomfort. Some patients may also be kept in the hospital for monitoring. Although PSVT can often be cured via a catheter ablation procedure, this is invasive (involving wires inserted via veins in the groin), so not everyone wishes to pursue this, and in some cases, it cannot be performed safely. There is a need for a rapid, safe, and effective treatment that patients can administer at home when PSVT occurs. Etripamil shows promise. Because it is a nasal spray, etripamil allows rapid absorption into the body ­ much faster than a tablet. Etripamil is not yet available on the market; however, several studies have demonstrated its effectiveness and safety, so it may be available in the near future. Promising evidence for etripamil in certain groups, such as elderly patients, is still lacking.

Cost, Efficiency and Outcomes of Pulsed Field Ablation versus Thermal Ablation for Atrial Fibrillation: A Real World Study.

BACKGROUND: With the exponential growth of catheter ablation (CA) for atrial fibrillation (AF), there is increasing interest in associated healthcare costs. Pulsed field ablation (PFA) using a single-shot pentaspline multi-electrode catheter has been shown to be safe and effective for AF CA, but its cost efficiency compared to conventional thermal ablation modalities (cryoballoon [CB] or radiofrequency [RF]) has not been evaluated. OBJECTIVE: To compare cost, efficiency, effectiveness and safety between PFA, CB and RF for AF ablation. METHODS: We studied 707 consecutive patients (208 PFA, 325 CB, 174 RF) undergoing first-time AF ablation. Individual procedural costs were calculated, including equipment, lab utilisation and hospital stay, and compared between ablation modalities, as effectiveness and safety. RESULTS: Skin-to-skin times and catheter lab times were significantly shorter with PFA (68min/102min) vs CB (91min/122min) and RF (89min/123 min); p<0.001. General anaesthesia utilisation differed across modalities (PFA 100%, CB 10.2%, RF 61.5%); p<0.001. Major complications occurred in 1% of cases, with no significant differences between modalities. Shorter procedural times resulted in lower staffing and lab costs with PFA, but these savings were offset by substantially higher equipment costs, resulting in higher overall median costs with PFA (£10,010) vs CB (£8,106) and RF (£8,949); p<0.001. CONCLUSION: In this contemporary real-world study of the three major AF CA modalities used concurrently, PFA had shorter skin-to-skin and catheter lab times than CB and RF, with similarly low rates of complications. However, PFA procedures were considerably more expensive, largely due to higher equipment cost.

Delineating postinfarct ventricular tachycardia substrate with dynamic voltage mapping in areas of omnipolar vector disarray.

Background: Defining postinfarct ventricular arrhythmic substrate is challenging with voltage mapping alone, though it may be improved in combination with an activation map. Omnipolar technology on the EnSite X system displays activation as vectors that can be superimposed onto a voltage map. Objective: The study sought to optimize voltage map settings during ventricular tachycardia (VT) ablation, adjusting them dynamically using omnipolar vectors. Methods: Consecutive patients undergoing substrate mapping were retrospectively studied. We categorized omnipolar vectors as uniform when pointing in one direction, or in disarray when pointing in multiple directions. We superimposed vectors onto voltage maps colored purple in tissue >1.5 mV, and the voltage settings were adjusted so that uniform vectors appeared within purple voltages, a process termed dynamic voltage mapping (DVM). Vectors in disarray appeared within red-blue lower voltages. Results: A total of 17 substrate maps were studied in 14 patients (mean age 63 ± 13 years; mean left ventricular ejection fraction 35 ± 6%, median 4 [interquartile range 2-8.5] recent VT episodes). The DVM mean voltage threshold that differentiated tissue supporting uniform vectors from disarray was 0.27 mV, ranging between patients from 0.18 to 0.50 mV, with good interobserver agreement (median difference: 0.00 mV). We found that VT isthmus components, as well as sites of latest activation, isochronal crowding, and excellent pace maps colocated with tissue along the DVM border zone surrounding areas of disarray. Conclusion: DVM, guided by areas of omnipolar vector disarray, allows for individualized postinfarct ventricular substrate characterization. Tissue bordering areas of disarray may harbor greater arrhythmogenic potential.

Durability of thermal pulmonary vein isolation in persistent atrial fibrillation assessed by a mandated repeat invasive study.

BACKGROUND: No study has assessed the durability of pulmonary vein isolation (PVI) with radiofrequency (RF) and cryoballoon (CB) in patients with persistent atrial fibrillation. These data are especially lacking for those with a significantly diseased left atrium (LA). OBJECTIVES: The goals of this study were to assess PVI durability in patients with significant LA disease and to compare reconnection rates between RF and CB. METHODS: Forty-four patients (mean age 63 years; 77% male; median time since atrial fibrillation diagnosis 22.5 months; median indexed LA volume 36 mL/m2) were randomized 1:1 to RF (StablePoint catheter, Boston Scientific) or CB (Arctic Front Advance, Medtronic) PVI. A redo procedure using ultra-high-density electroanatomic mapping (Rhythmia, Boston Scientific) was mandated at 2 months, where PV reconnections were identified and reisolated. RESULTS: Thirty-eight patients underwent both procedures (CB n = 17; RF n = 21). Index RF procedures were longer (median 158 minutes vs 97 minutes; P < .001) but required less fluoroscopy (9.5 minutes vs 23 minutes; P < .001). At the index RF procedure, a median of 47% of the LA myocardium had voltage < 0.5 mV, suggesting that half of the mapped LA comprised scar. PV reconnection was observed in 73 of 152 PVs (48.0%) and was more frequent with CB (58.8%) than with RF (39.3%) (P = .022). Reconnection of at least 1 PV was detected in >75% of patients. Significantly more ablation was required at the redo procedure to reisolate PVs in the CB arm (median 10.8 minutes vs 1.2 minutes; P < .001). CONCLUSION: PVI durability may be poor in those with significant LA scarring and dilatation, even with modern thermal ablation technologies. RF resulted in significantly better PVI durability than did CB in this complex population. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT04111731.

Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Lesion metrics and 12-month outcomes of very-high power short duration radiofrequency ablation (90W/4 s) under mild conscious sedation.

INTRODUCTION: Pulmonary vein isolation (PVI) is often performed under general anaesthesia (GA) or deep sedation. Anaesthetic availability is limited in many centers, and deep sedation is prohibited in some countries without anaesthetic support. Very high-power short duration (vHPSD-90W/4 s) PVI using the Q-Dot catheter is generally well tolerated under mild conscious sedation (MCS) though an understanding of catheter stability and long-term effectiveness is lacking. We analyzed lesion metrics and 12-month freedom from atrial arrythmia with this approach. METHODS: Our approach to radiofrequency (RF) PVI under MCS is standardized and includes a single catheter approach with a steerable sheath. We identified patients undergoing Q-Dot RF PVI between March 2021 and December 2022 in our center, comparing those undergoing vHPSD ablation under MCS (90W/MCS) against those undergoing 50 W ablation under GA (50 W/GA) up to 12 months of follow-up. Data were extracted from clinical records and the CARTO system. RESULTS: Eighty-three patients met our inclusion criteria (51 90W/MCS; 32 50 W/GA). Despite shorter ablation times (353 vs. 886 s; p < .001), the 90 W/MCS group received more lesions (median 87 vs. 58, p < .001), resulting in similar procedure times (149.3 vs. 149.1 min; p = .981). PVI was achieved in all cases, and first pass isolation rates were similar (left wide antral circumferential ablation [WACA] 82.4% vs. 87.5%, p = .758; right WACA 74.5% vs. 78.1%, p = .796; 90 W/MCS vs. 50 W/GA respectively). Analysis of 6647 ablation lesions found similar mean impedance drops (10.0 ± 1.9 Ω vs. 10.0 ± 2.2 Ω; p = .989) and mean contact force (14.6 ± 2.0 g vs. 15.1 ± 1.6 g; p = .248). Only median 2.5% of lesions in the 90 W/MCS cohort failed to achieve ≥ 5 Ω drop. In the 90 W/MCS group, there were no procedural related complications, and 12-month freedom from atrial arrhythmia was observed in 78.4%. CONCLUSION: vHPSD PVI is feasible under MCS, with encouraging acute and long-term procedural outcomes. This provides a compelling option for centers with limited anaesthetic support.

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial.

BACKGROUND: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. METHODS: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence > 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications. RESULTS: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43-2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29-0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). CONCLUSION: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF.

Novel stroke prevention strategies following catheter ablation for atrial fibrillation.

Stroke prevention following successful catheter ablation of atrial fibrillation remains a controversial topic. Oral anticoagulation is associated with a significant reduction in stroke risk in the general atrial fibrillation population but may be associated with an increased risk of major bleeding, and the benefit: risk ratio must be considered. Improvement in successful catheter ablation and widespread use of cardiac monitoring devices may allow for novel anticoagulation strategies in a subset of patients with atrial fibrillation, which may optimize stroke prevention while minimizing bleeding risk. In this review, we discuss stroke risk in atrial fibrillation and the effects of successful catheter ablation on thromboembolic risk. We also explore novel strategies for stroke prevention following successful catheter ablation.

Predicting stroke in Asian patients with atrial fibrillation using machine learning: A report from the KERALA-AF registry, with external validation in the APHRS-AF registry.

Atrial fibrillation (AF) is a significant risk factor for stroke. Based on the higher stroke associated with AF in the South Asian population, we constructed a one-year stroke prediction model using machine learning (ML) methods in KERALA-AF South Asian cohort. External validation was performed in the prospective APHRS-AF registry. We studied 2101 patients and 83 were to patients with stroke in KERALA-AF registry. The random forest showed the best predictive performance in the internal validation with receiver operator characteristic curve (AUC) and G-mean of 0.821 and 0.427, respectively. In the external validation, the light gradient boosting machine showed the best predictive performance with AUC and G-mean of 0.670 and 0.083, respectively. We report the first demonstration of ML's applicability in an Indian prospective cohort, although the more modest prediction on external validation in a separate multinational Asian registry suggests the need for ethnic-specific ML models.

Silent pulmonary veins at redo ablation for atrial fibrillation: Implications and approaches.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Despite promising success rates, redo ablation is sometimes required. At redo, PVs may be found to be isolated (silent) or reconnected. We studied patients with silent vs reconnected PVs at redo and analysed associations with adverse outcomes. METHODS: Patients undergoing redo AF ablations between 2013 and 2019 at our institution were included and stratified into silent PVs or reconnected PVs. The primary outcome was a composite of further redo ablation, non-AF ablation, atrioventricular nodal ablation, and death. Secondary outcomes included arrhythmia recurrence. RESULTS: A total of 467 patients were included with mean 4.6 ± 1.7 years follow-up, of whom 48 (10.3%) had silent PVs. The silent PV group had had more often undergone >1 prior ablation (45.8% vs 9.8%; p<0.001), had more persistent AF (62.5% vs 41.1%; p=0.005) and had more non-PV ablation performed both at prior ablation procedures and at the analysed redo ablation. The primary outcome occurred more frequently in those with silent PVs (25% vs 13.8%; p=0.053). Arrhythmia recurrence was also more common in the silent PV group (66.7% vs 50.6%; p=0.047). After multivariable adjustment, female sex (aHR 2.35 [95% CI 2.35-3.96]; p=0.001) and ischaemic heart disease (aHR 3.21 [95% CI 1.56-6.62]; p=0.002) were independently associated with the primary outcome, and left atrial enlargement (aHR 1.58 [95% CI 1.20-2.08]; p=0.001) and >1 prior ablation (aHR 1.88 [95% CI 1.30-2.72]; p<0.001) were independently associated with arrhythmia recurrence. Whilst a finding of silent PVs was not itself significant after multivariable adjustment, this provides an easily assessable parameter at clinically indicated redo ablation which informs the clinician of the likelihood of a worse future prognosis. CONCLUSIONS: Patients with silent PVs at redo AF ablation have worse clinical outcomes.

Concurrent percutaneous left atrial appendage occlusion and catheter ablation for atrial fibrillation: State-of-the-art review.

Stroke prevention and symptom control are two integral pillars in atrial fibrillation (AF) management. Percutaneous left atrial appendage occlusion (LAAO) is effective at reducing stroke risk in high-risk patients with AF who cannot tolerate oral anticoagulant therapy, whilst catheter ablation is effective at reducing AF burden and improving quality-of-life in patients who remain symptomatic despite medical therapy. If both procedures are indicated in an individual patient, they have traditionally been performed on separate occasions, due to long cumulative procedural times, itself associated with thromboembolic risk. Recently, with the advancement of procedural techniques, the concept of concurrent LAAO and AF catheter ablation has gained traction. This review summarises the evidence for and against concurrent LAAO and AF catheter ablation, discussing procedural considerations, including procedural sequencing and post-procedural antithrombotic therapy, safety and efficacy outcomes, and future directions in the field.

Hydrophobic interaction between the TM1 and H8 is essential for rhodopsin trafficking to vertebrate photoreceptor outer segments.

A major unsolved question in vertebrate photoreceptor biology is the mechanism of rhodopsin transport to the outer segment. In rhodopsin-like class A G protein-coupled receptors, hydrophobic interactions between C-terminal α-helix 8 (H8), and transmembrane α-helix-1 (TM1) have been shown to be important for transport to the plasma membrane, however whether this interaction is important for rhodopsin transport to ciliary rod outer segments is not known. We examined the crystal structures of vertebrate rhodopsins and class A G protein-coupled receptors and found a conserved network of predicted hydrophobic interactions. In Xenopus rhodopsin (xRho), this interaction corresponds to F313, L317, and L321 in H8 and M57, V61, and L68 in TM1. To evaluate the role of H8-TM1 hydrophobic interactions in rhodopsin transport, we expressed xRho-EGFP where hydrophobic residues were mutated in Xenopus rods and evaluated the efficiency of outer segment enrichment. We found that substituting L317 and M57 with hydrophilic residues had the strongest impact on xRho mislocalization. Substituting hydrophilic amino acids at positions L68, F313, and L321 also had a significant impact. Replacing L317 with M resulted in significant mislocalization, indicating that the hydrophobic interaction between residues 317 and 57 is exquisitely sensitive. The corresponding experiment in bovine rhodopsin expressed in HEK293 cells had a similar effect, showing that the H8-TM1 hydrophobic network is essential for rhodopsin transport in mammalian species. Thus, for the first time, we show that a hydrophobic interaction between H8 and TM1 is critical for efficient rhodopsin transport to the vertebrate photoreceptor ciliary outer segment.

Balancing the risk of stroke and bleeding in atrial fibrillation patients with a history of falls.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and can lead to serious consequences such as ischemic stroke and systemic thromboembolism. The risk of thromboembolism can be reduced by anticoagulation, however many patients with high falls risk do not receive oral anticoagulation. AREAS COVERED: In this narrative literature review, performed with searches of the PubMed database, we discuss the factors predisposing AF patients to falls, ways to optimize bleeding risk with individualized assessment, and clarify misconceptions around falls risk and anticoagulation therapy. EXPERT OPINION: In general, the advantages of stroke prevention with oral anticoagulation outweigh the risk of bleeding resulting from falls, especially with the increasing use of non-vitamin K oral anticoagulants, which are associated with fewer intracranial hemorrhages and thromboembolic complications than vitamin K anticoagulants. Most studies in this field are observational and randomized controlled studies would be beneficial.

Sex Differences in Atrial Fibrillation.

PURPOSE OF REVIEW: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The estimated lifetime risk of developing AF is higher in men; however, due to differences in life expectancy, the overall prevalence is higher among women, particularly in the older age group. Sex differences play an important role in the pathophysiology, presentation, and clinical outcomes of AF. Awareness of these differences minimizes the potential for disparities in AF management. Our review summarizes the current literature on sex differences in AF, including the epidemiology, pathophysiology, risk factors, clinical symptomatology, mechanisms, treatment, and outcomes. We also explore the implications of these differences for clinical practice and future research. RECENT FINDINGS: Women are more likely to present with atypical symptoms, have a higher stroke risk, and have a worse quality of life with AF when compared to men. Despite this, they are less likely to receive rhythm control strategies and anticoagulants. The sex-based differences in AF pathology and management might be a combination of inherent biological and hormonal differences, and implicit bias of the research entities and treating clinicians. Our review stresses the need for further sex-specific research in the pathophysiology of AF and opens a dialogue on personalized medicine, where management strategies can be tailored to individual patient characteristics, including sex.

Silent cerebral lesions following catheter ablation for atrial fibrillation: a state-of-the-art review.

Atrial fibrillation is associated with neurocognitive comorbidities such as stroke and dementia. Evidence suggests that rhythm control-especially if implemented early-may reduce the risk of cognitive decline. Catheter ablation is highly efficacious for restoring sinus rhythm in the setting of atrial fibrillation; however, ablation within the left atrium has been shown to result in MRI-detected silent cerebral lesions. In this state-of-the-art review article, we discuss the balance of risk between left atrial ablation and rhythm control. We highlight suggestions to lower the risk, as well as the evidence behind newer forms of ablation such as very high power short duration radiofrequency ablation and pulsed field ablation.

Percutaneous left atrial appendage occlusion following successful treatment of large bi-atrial thrombi in a patient with atrial fibrillation: a case report.

Background: Atrial fibrillation (AF) is a well-established risk factor for intracardiac thrombosis. Left atrial appendage occlusion (LAAO) is emerging as a viable alternative to oral anticoagulation (OAC) for high-risk AF patients who are contraindicated to long-term OAC. Case summary: A 74-year-old man with a history of permanent AF and subdural haemorrhage on warfarin therapy was referred to our facility for further management. Cardiac CT imaging revealed large bi-atrial thrombi for which apixaban therapy was initiated. Serial imaging over nine months showed gradual shrinkage and then resolution of the thrombi. In line with the patient's preference to avoid life-long OAC, he received LAAO using an Amplatzer™ Amulet™ device. Follow-up transoesophageal echocardiography showed a well-seated device with no leak and no thrombus. Discussion: We discussed the key issues surrounding management of bi-atrial thrombi and the decision to perform LAAO in these circumstances, relying on shared decision making and multi-disciplinary team input.