Randomized Study Comparing Radiofrequency Ablation with the PVAC Gold System vs. Antiarrhythmic Drugs in Elderly Patients with Symptomatic Atrial Fibrillation. / Estudo Randomizado Comparando a Ablação por Cateter com o PVAC Gold vs. Tratamento com Fármacos Antiarrítmicos em Pacientes Idosos com Fibrilação Atrial Sintomática.

BACKGROUND: There are no randomized studies comparing the maintenance of sinus rhythm after catheter ablation (CA) concerning treatment with antiarrhythmic drugs (AA) in elderly patients with paroxysmal atrial fibrillation (AF). OBJECTIVES: To compare the clinical results of pulmonary vein (PV) isolation with the second-generation PVAC Gold catheter against AA treatment in elderly people with recurrent symptomatic paroxysmal AF, refractory to at least one AA, and without structural heart disease. METHODS: Sixty patients with paroxysmal AF ≥ 65 years old were randomized to two forms of treatment: group 1: CA and group 2: AA drugs. The primary outcome was the AF recurrence-free rate after at least one year of follow-up. Secondary outcomes were: progression to persistent forms of AF, impact on quality of life (QOLF), and complications. The significance level adopted in the statistical analysis was 5% (p<0.05). RESULTS: The AF recurrence-free rate was 80% (10% with amiodarone) in the CA group, after 1.3 procedures per patient and 65% in the AA group (60% with amiodarone), (p = 0.119) in an average follow-up of 719 days (Q1: 566; Q3: 730). The persistent AF free rate was 83.4% in the AC group and 67.7% in the AA group (p = 0.073) Both strategies showed an improvement in the AFQoL score during follow-up (p < 0.001), with no difference between the groups. Although without clinical repercussions or impact on the intellectual assessment test, 25% of patients in the CA group showed signs of cerebral embolization on brain MRI. CONCLUSIONS: Both strategies for maintaining sinus rhythm promoted an improvement in the quality of life of elderly patients with symptomatic AF, with no statistical difference in the clinical outcomes. Additional studies using technologies with a better safety profile are needed to evaluate the benefits of CA in elderly patients with AF.

FUNDAMENTO: Não existem estudos randomizados comparando a manutenção do ritmo sinusal após ablação por cateter (AC) em relação ao tratamento com fármacos antiarrítmicos (AA) em pacientes idosos portadores fibrilação atrial (FA) paroxística. OBJETIVOS: Comparar os resultados clínicos do isolamento das veias pulmonares (VPs) com o cateter PVAC Gold de segunda geração com o uso de AA em idosos com FA paroxística sintomática, recorrente, apesar do uso de fármacos AA. MÉTODOS: Sessenta pacientes com FA paroxística ≥ 65 anos e sem cardiopatias estruturais foram randomizados para duas formas de tratamento: grupo 1: AC e grupo 2: AA. O desfecho primário foi a taxa livre de recorrência de FA após pelo menos um ano de seguimento. Os desfechos secundários foram: progressão para formas persistentes de FA, impacto na qualidade de vida (QVFA) e complicações. O nível de significância adotado na análise estatística foi de 5% (p<0,05). RESULTADOS: A taxa livre de recorrência de FA foi de 80% (10% com amiodarona) no grupo AC, após 1,3 procedimentos por paciente e de 65% no grupo AA (60% com amiodarona), (p = 0,119) num seguimento médio de 719 dias (Q1: 566; Q3: 730). A taxa livre de FA persistente foi de 83,4% no grupo AC e de 67,7% no grupo AA (p = 0,073). Ambas as estratégias apresentaram melhora no escore de QVFA durante o seguimento (p < 0,001), sem diferença entre os grupos. Embora sem repercussão clínica ou impacto no teste de avaliação intelectual, 25% dos pacientes do grupo PVAC apresentou sinais de embolização cerebral na RNM cerebral. CONCLUSÕES: Ambas as estratégias para manutenção do ritmo sinusal promoveram melhora na qualidade de vida de pacientes idosos com FA sintomática, sem diferença estatística nos desfechos clínicos preconizados. Estudos adicionais usando tecnologias com melhor perfil de segurança são necessários para avaliar os benefícios da AC em pacientes idosos com FA.

Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of neuropeptide Y on long-term reinduction of atrial fibrillation.

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.

An Underestimated Cause of Hemoptysis in a 41-Year-Old Man.

CASE PRESENTATION: A 41-year-old man who currently smokes with previous sporadic use of cocaine and cannabinoids was admitted at the hospital suffering from hemoptysis which had developed 4 days before. The patient was on anticoagulant therapy with rivaroxaban due to paroxysmal atrial fibrillation diagnosed in 2018, for which he had undergone pulmonary vein electrical isolation by radiofrequency and ablation of cavotricuspid isthmus in January 2019. The procedure was completed in July 2019. Treatment with flecainide was introduced due to recurrences of atrial fibrillation. In February 2021, a new attempt at ablation was performed by electrical isolation of the left atrial posterior wall. The latest cardiologic checkup documented an echocardiographic framework of mild left atrial dilatation and normal-sized right ventricle with longitudinal shortening index at the lower limits, and a recurrence of asymptomatic atrial fibrillation at Holter ECG (March 2022).

Pulmonary Vein Thrombus After Mitral Valve Transcatheter Edge-to-Edge Repair.

A 76-year-old female with a complicated medical history presented for Watchman (Boston Scientific) placement 2 months after mitral valve transcatheter edge-to-edge repair (TEER). Preoperative workup before Watchman placement confirmed the presence of a thrombus in the left superior pulmonary vein. Post-procedure mitral valve TEER transesophageal echocardiogram showed no thrombus in the left atrium appendage or pulmonary veins. We believe the thrombus in the left superior pulmonary vein occurred secondarily due to epithelium damage during the mitral valve TEER.

[Mispositioned central line with catheterization of partial anomalous pulmonary venous return]. / Voie centrale mal positionnée avec cathétérisme d'un retour veineux pulmonaire anormal partiel.

Central venous access is common practice in intensive care, anesthesia and emergency departments. It is, however, a delicate technical procedure, prone to complications. We present a case report on the placement of a left jugular central venous line in the emergency room, which was thought to be a routine procedure. However, the operator observed arterial blood during sampling, and the central line was described as poorly positioned on the control X-ray. After verification and other examinations, the existence of a vertical vein was discovered in this patient, connecting the left superior pulmonary vein to the brachiocephalic trunk. A poorly positioned central venous line can therefore lead to the discovery of asympomatic congenital vascular anomalies, unrelated to the clinical context. This case study illustrates the various tools available to ensure the correct position of a central venous line, and their clinical implications.

La mise en place d'une voie veineuse centrale est de pratique courante aux soins intensifs, en anesthésie et aux urgences. Il s'agit cependant d'un acte technique relativement invasif, délicat et potentiellement sujet à complications. Nous présentons un cas clinique relatant la mise en place d'une voie veineuse centrale jugulaire gauche en salle de déchocage, manœuvre réputée banale. Cependant, l'opérateur objective visuellement du sang d'allure artérielle lors du prélèvement sanguin sur le cathéter. En outre, l'imagerie par radiographie thoracique décrit une malposition de ce dispositif. Après vérifications et examens complémentaires, nous découvrons finalement l'existence d'une veine verticale chez ce patient, reliant la veine pulmonaire supérieure gauche au tronc brachio-céphalique. Une voie veineuse centrale, apparemment mal positionnée, peut, dès lors, conduire à la découverte d'anomalies vasculaires congénitales asymptomatiques, sans lien nécessaire avec le contexte clinique sous-jacent. Ce cas clinique nous permet d'aborder les différents outils à notre disposition actuelle afin de déterminer le positionnement adéquat d'une voie veineuse centrale et les implications cliniques qui en découlent.

Incremental Benefit of Stepwise Nonpulmonary Vein Trigger Provocation During Catheter Ablation of Atrial Fibrillation.

BACKGROUND: The importance of nonpulmonary vein (PV) triggers for the initiation/recurrence of atrial fibrillation (AF) is well established. OBJECTIVES: This study sought to assess the incremental benefit of provocative maneuvers for identifying non-PV triggers. METHODS: We included consecutive patients undergoing first-time AF ablation between 2020 and 2022. The provocation protocol included step 1, identification of spontaneous non-PV triggers after cardioversion of AF and/or during sinus rhythm; step 2, isoproterenol infusion (3, 6, 12, and 20-30 µg/min); and step 3, atrial burst pacing to induce AF followed by cardioversion during residual or low-dose isoproterenol infusion or induce focal atrial tachycardia. Non-PV triggers were defined as non-PV ectopic beats triggering AF or sustained focal atrial tachycardia. RESULTS: Of 1,372 patients included, 883 (64.4%) underwent the complete stepwise provocation protocol with isoproterenol infusion and burst pacing, 334 (24.3%) isoproterenol infusion only, 77 (5.6%) burst pacing only, and 78 (5.7%) no provocative maneuvers (only step 1). Overall, 161 non-PV triggers were found in 135 (9.8%) patients. Of these, 51 (31.7%) non-PV triggers occurred spontaneously, and the remaining 110 (68.3%) required provocative maneuvers for induction. Among those receiving the complete stepwise provocation protocol, there was a 2.2-fold increase in the number of patients with non-PV triggers after isoproterenol infusion, and the addition of burst pacing after isoproterenol infusion led to a total increase of 3.6-fold with the complete stepwise provocation protocol. CONCLUSIONS: The majority of non-PV triggers require provocative maneuvers for induction. A stepwise provocation protocol consisting of isoproterenol infusion followed by burst pacing identifies a 3.6-fold higher number of patients with non-PV triggers.

Diagnosis to Ablation in Persistent AF: Any Time Can Be a Good Time to Ablate.

BACKGROUND: Nonrandomized data suggest that longer diagnosis-to-ablation time (DAT) is associated with poorer outcomes; however, a recent randomized trial found no difference in recurrences when ablation was delayed by 12 months. OBJECTIVES: This study sought to assess the impact of DAT on atrial fibrillation (AF) recurrence in patients undergoing catheter ablation for persistent AF. METHODS: CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA randomized clinical trial) was a multicenter trial that randomized patients with persistent AF to pulmonary vein isolation + posterior wall isolation or pulmonary vein isolation alone. Follow-up was 12 months. Outcomes were assessed after a 3-month blanking period. RESULTS: Median DAT in the 334 patients was 28 months (Q1-Q3: 12-66 months). Patients were divided into quartile groups: Q1 was DAT 0 to 12 months (n = 84, median DAT 7 months), Q2 was DAT 13 to 28 months (n = 85, median DAT 20 months), Q3 was DAT 29 to 66 months (n = 84, median DAT 41 months), and Q4 was DAT ≥67 months (n = 81, median DAT 119 months). AF recurrence rate was 36.9% for Q1, 44.7% for Q2, 47.6% for Q3, and 56.8% for Q4 (P = 0.082). On multivariable analysis, DAT Q4 was the only factor significantly associated with risk of recurrence (HR: 1.607; 95% CI: 1.005-2.570; P = 0.048). Median AF burden was 0% (Q1-Q3: 0%-0.47%) in Q1 and 0.33% (Q1-Q3: 0%-4.6%) in Q4 (P = 0.002). Quality of life (assessed by the Atrial Fibrillation Effect on Quality-of-Life questionnaire) improved markedly in all quartiles (Q1: Δ28.8 ± 24, Q2: Δ24.4 ± 23.4, Q3: Δ21.7 ± 26.6, Q4: Δ24.6 ± 21.4; P = 0.331). CONCLUSIONS: In a cohort of patients with persistent AF undergoing ablation in a prospective trial with standardized entry criteria and intensive electrocardiogram monitoring, those with shorter DAT had lower rates of AF recurrence. However, differences were modest, and all quartiles demonstrated very low AF burden and improvements in quality of life.

Hybrid-Convergent Procedure or Pulsed Field Ablation in Long-Standing Persistent Atrial Fibrillation.

BACKGROUND: Hybrid-convergent radiofrequency (RF) ablation targeting pulmonary veins (PVs) and left atrial posterior wall (LAPW) has shown better arrhythmic outcomes than an endocardial-only RF strategy, despite higher rates of complications. Comparisons with extensive pulsed field ablation (PFA) are currently lacking. OBJECTIVES: This study aimed to compare the efficacy and safety of the hybrid-convergent RF vs PFA of PVs and LAPW in long-standing persistent atrial fibrillation (LSPAF). METHODS: Ninety-three consecutive LSPAF patients, treated with 2-step hybrid-convergent RF ablation (hybrid group, n = 49) or with PFA of PVs and LAPW (PFA group, n = 44) were enrolled. Primary efficacy endpoint was defined as any atrial tachyarrhythmias (ATA) recurrence after the 3-month blanking period, over a follow-up time of 12 months. Periprocedural adverse events and late complications during follow-up were deemed primary safety outcomes. RESULTS: The hybrid and PFA groups had similar baseline characteristics; mean age was hybrid 63.8 ± 10.6 years vs PFA 66.0 ± 7.4 years; P = 0.105. PV and LAPW ablation were acutely successful in all patients. Step 1 hybrid-epicardial procedures were longer than PFA (166 [Q1-Q3: 140-205] minutes vs 107.5 [Q1-Q3: 82.5-12] minutes; P < 0.01). At 12-month follow-up, there was no difference in ATA recurrences between groups (hybrid 36.7% vs PFA 40.9%; P = 0.680; log-rank at survival analysis P = 0.539). After adjusting for confounders, a larger left atrial volume and recurrences during the blanking-period were predictors of ATA recurrences after ablation, regardless of procedural technique employed. PFA showed a better safety profile with a lower rate of major periprocedural complications compared with hybrid ablation (12% vs 0%; P = 0.028). CONCLUSIONS: Hybrid-convergent and PFA share comparable arrhythmic outcomes in LSPAF, but hybrid-convergent ablation carries higher periprocedural risks.

Initial experience with zero-fluoroscopy pulmonary vein isolation in patients with atrial fibrillation: single-center observational trial.

Pulmonary vein isolation (PVI) stands as a widely practiced cardiac ablation procedure on a global scale, conventionally guided by fluoroscopy. The concurrent application of electroanatomical mapping systems (EAMS) and intracardiac echocardiography offers a means to curtail radiation exposure. This study aimed to compare procedural outcomes between conventional and our initial zero-fluoroscopy cases in patients with paroxysmal or persistent atrial fibrillation (AF), undergoing point-by-point PVI. Our prospective observational study included 100 consecutive patients with AF who underwent point-by-point radiofrequency PVI. The standard technique was used in the first 50 cases (Standard group), while the fluoroless technique was used in the subsequent 50 patients (Zero group). The zero-fluoroscopy approach exhibited significantly shorter procedural time (59.6 ± 10.7 min vs. 74.6 ± 13.2 min, p < 0.0001), attributed to a reduced access time (17 [16; 20] min vs. 31 [23; 34.5] min, p < 0.001). Comparable results were found for the number of RF applications, total ablation energy, and left atrial dwelling time. In the Zero group, all procedures were achieved without fluoroscopy, resulting in significantly lower fluoroscopy time (0 [0; 0] sec vs. 132 [100; 160] sec, p < 0.0001) and dose (0 [0; 0] mGy vs. 4.8 [4.1; 8.2] mGy, p < 0.0001). The acute success rate was 100%, with no major complications. Zero-fluoroscopy PVI is feasible, safe, and associated with shorter procedure times compared to the standard approach, even in cases without prior experience in zero-fluoroscopy PVI.

Pulmonary vein isolation using pulsed field ablation vs. high-power short-duration radiofrequency ablation in paroxysmal atrial fibrillation: efficacy, safety, and long-term follow-up (PRIORI study).

AIMS: Pulsed field ablation (PFA) is a novel, non-thermal, cardiac tissue-selective ablation modality. To date, radiofrequency (RF)-guided high-power short-duration (HPSD) ablation represents the gold standard besides cryo-ablation for pulmonary vein isolation (PVI). This single-centre, retrospective study investigated the efficacy of PFA-PVI vs. HPSD-RF PVI in terms of single-procedure arrhythmia-free outcome and safety in a real-world setting. METHODS AND RESULTS: Consecutive, paroxysmal atrial fibrillation (AF) patients who underwent PVI using PFA or HPSD-RF were enrolled. In group PFA, PVI was performed using a pentaspline PFA catheter. The ablation procedure in group HPSD-RF was performed with RF energy (45 W, ablation index). A total of 410 patients (group PFA, 201; group HPSD-RF, 209) were included. There was no difference between both groups regarding age, gender, and CHA2DS2-VASc score. The procedure time was significantly shorter in group PFA [61 (44-103) vs. 125 (105-143) min; P < 0.001]; fluoroscopy time and dose area product were significantly higher in group PFA [16 (13-20) vs. 4 (2-5) min; P < 0.01 and 412 (270-739) vs. 129 (58-265) µGym2; P < 0.01]. The overall complication rates were 2.9% in group PFA and 6.2% in group HPSD (P = 0.158). There was one fatal stroke in the PFA group. The 1-year Kaplan-Meier estimated freedom from any atrial tachyarrhythmia was 85% with PFA and 79% with HPSD-RF (log-rank P = 0.160). In 56 repeat ablation procedures, the PV reconnection rate was 30% after PFA and 38% after HPSD-RF (P = 0.372). CONCLUSION: Both PFA and HPSD-RF were highly efficient and effective in achieving PVI in paroxysmal AF patients. The arrhythmia-free survival is comparable. The PV reconnection rate was not different.

A possible path to persistent re-entry waves at the outlet of the left pulmonary vein.

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, often evolving from paroxysmal episodes to persistent stages over an extended timeframe. While various factors contribute to this progression, the precise biophysical mechanisms driving it remain unclear. Here we explore how rapid firing of cardiomyocytes at the outlet of the pulmonary vein of the left atria can create a substrate for a persistent re-entry wave. This is grounded in a recently formulated mathematical model of the regulation of calcium ion channel density by intracellular calcium concentration. According to the model, the number of calcium channels is controlled by the intracellular calcium concentration. In particular, if the concentration increases above a certain target level, the calcium current is weakened to restore the target level of calcium. During rapid pacing, the intracellular calcium concentration of the cardiomyocytes increases leading to a substantial reduction of the calcium current across the membrane of the myocytes, which again reduces the action potential duration. In a spatially resolved cell-based model of the outlet of the pulmonary vein of the left atria, we show that the reduced action potential duration can lead to re-entry. Initiated by rapid pacing, often stemming from paroxysmal AF episodes lasting several days, the reduction in calcium current is a critical factor. Our findings illustrate how such episodes can foster a conducive environment for persistent AF through electrical remodeling, characterized by diminished calcium currents. This underscores the importance of promptly addressing early AF episodes to prevent their progression to chronic stages.

Left ventricular dysfunction in pulmonary arterial hypertension is attributed to underfilling rather than intrinsic myocardial disease: a CMR 2D phase contrast study.

The pathophysiology underlying impaired LV function in PAH remains unclear, with some studies implicating intrinsic myocardial dysfunction and others pointing to LV underfilling. Evaluation of pulmonary vein area (PVA) and flow may offer novel, mechanistic insight by distinguishing elevated LV filling pressure common in myocardial dysfunction from LV underfilling. This study aimed to elucidate LV filling physiology in PAH by assessing PVA and flow using cardiac magnetic resonance (CMR) and compare pulmonary vein flow in PAH with HFrEF as a model representing elevated filling pressures, in addition to healthy controls. Patients with PAH or heart failure with reduced ejection fraction (HFrEF) referred for CMR were retrospectively reviewed, and healthy controls were included as reference. Pulmonary vein S, D and A-wave were compared between groups. Associations between pulmonary vein area (PVA) by CMR and echocardiographic indices of LV filling pressure were evaluated. Nineteen patients with PAH, 25 with HFrEF and 24 controls were included. Both PAH and HFrEF had lower ejection fraction and S-wave velocity than controls. PAH displayed smaller LV end-diastolic volumes than controls, while HFrEF demonstrated larger PVA and higher A-wave reversal. PVA was associated with mitral E/e' ratio (r2 = 0.10; p = 0.03), e' velocity (r2 = 0.23; p = 0.001) and left atrial volume (r2 = 0.07; p = 0.005). Among PAH, PVA was not associated with LV-GLS. A PVA cut-off of 2.3cm2 displayed 87% sensitivity and 72% specificity to differentiate HFrEF and PAH (AUC = 0.82). PAH displayed lower pulmonary vein S-wave velocity, smaller LV volume and reduced function compared with controls. Reduced LV function in PAH may be owing to underfilling rather than intrinsic myocardial disease. PVA demonstrates promise as a novel, non-invasive imaging marker to assess LV filling status.

Adjunctive left atrial posterior wall isolation for atrial fibrillation: An updated systematic review and meta-analysis.

OBJECTIVE: Posterior left atrial wall isolation (PWI) plus traditional pulmonary vein isolation (PVI) has been proposed as a promising intervention to decrease atrial fibrillation (AF) recurrence. We aim to investigate the efficacy and safety of adding PWI to the traditional PVI in patients with AF. METHODS: A systematic review and meta-analysis was conducted using synthesizing randomized controlled trials (RCTs) retrieved by systematically searching PubMed, Web of Science, SCOPUS, EMBASE, and Cochrane through June 14, 2023. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023446227). RESULTS: We included 11 RCTs with a total number of 1534 patients. Combined ablation with PWI + PVI was not associated with any significant difference over PVI only regarding the recurrence of clinical AF (RR: 0.86 with 95% CI [0.70-1.06]), all atrial arrhythmia (RR: 0.93 with 95% CI [0.82-1.07]), nonatrial fibrillation arrhythmia (RR: 1.22 with 95% CI [0.97-1.53]), early AF (RR: 0.89 with 95% CI [0.62-1.27]), and antiarrhythmic drugs at discharge (RR: 0.83 with 95% CI [0.67-1.04]). However, it was associated with increased total ablation duration (minutes) (MD: 12.58 with 95% CI [6.80-18.37]) and total procedure duration (minutes) (MD: 16.77 with 95% CI [9.63-23.91]), without any significant difference regarding adverse events (RR: 1.05 with 95% CI [0.63-1.74]). CONCLUSION: While the pooled data from PWI + PVI using point-by-point radiofrequency did not suggest a benefit in the recurrence of various atrial arrhythmias compared to PVI alone, PWI+PVI using direct posterior wall ablation, especially with cryoballoon, demonstrated a significant reduction in recurrence of AF/atrial arrhythmias. Also, PWI + PVI significantly increased the ablation and total procedure durations.

A validation study of the accuracy of the atrial pace map assessed with intracardiac pattern matching: Potential utility of non-pulmonary vein mapping.

BACKGROUND: Identification of infrequent nonpulmonary vein trigger premature atrial contractions (PACs) is challenging. We hypothesized that pace mapping (PM) assessed by correlation scores calculated by an intracardiac pattern matching (ICPM) module was useful for locating PAC origins, and conducted a validation study to assess the accuracy of ICPM-guided PM. METHODS: Analyzed were 30 patients with atrial fibrillation. After pulmonary vein isolation, atrial pacing was performed at one or two of four sites on the anterior and posterior aspects of the left atrium (LA, n = 10/10), LA septum (n = 10), and lateral RA (n = 10), which was arbitrarily determined as PAC. The intracardiac activation obtained from each pacing was set as an ICPM reference consisting of six CS unipolar electrograms (CS group) or six CS unipolar electrograms and four RA electrograms (CS-RA group). RESULTS: The PM was performed at 193 ± 107 sites for each reference pacing site. All reference pacing sites corresponded to sites where the maximal ICPM correlation score was obtained. Sites with a correlation score ≥98% were rarely obtained in the CS-RA than CS group (33% vs. 55%, P = .04), but those ≥95% were similarly obtained between the two groups (93% vs. 88%, P = .71), and those ≥90% were obtained in all. The surface areas with correlation scores ≥98% (0[0,10] vs. 10[0,35] mm2, P = .02), ≥95% (10[10,30] vs. 50[10,180] mm2, P = .002) and ≥90% (60[30,100] vs. 170[100,560] mm2, P = .0002) were smaller in the CS-RA than CS group. CONCLUSIONS: ICPM-guided PM was useful for identifying the reference pacing sites. Combined use of RA and CS electrograms may improve the mapping quality.

A danish healthcare-focused economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation.

INTRODUCTION: Three randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective. METHODS: Individual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis. RESULTS: First-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon. CONCLUSION: First-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.

Atypical Antiadrenergic Effect of Refralon as a Mechanism of High Antiarrhythmic Effectiveness.

We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 µg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away.

Chronic Partial Sleep Deprivation Increased the Incidence of Atrial Fibrillation by Promoting Pulmonary Vein and Atrial Arrhythmogenesis in a Rodent Model.

Sleep deprivation (SD) is a recognized risk factor for atrial fibrillation (AF), yet the precise molecular and electrophysiological mechanisms behind SD-induced AF are unclear. This study explores the electrical and structural changes that contribute to AF in chronic partial SD. We induced chronic partial SD in Wistar rats using a modified multiple-platform method. Echocardiography demonstrated impaired systolic and diastolic function in the left ventricle (LV) of the SD rats. The SD rats exhibited an elevated heart rate and a higher low-frequency to high-frequency ratio in a heart-rate variability analysis. Rapid transesophageal atrial pacing led to a higher incidence of AF and longer mean AF durations in the SD rats. Conventional microelectrode recordings showed accelerated pulmonary vein (PV) spontaneous activity in SD rats, along with a heightened occurrence of delayed after-depolarizations in the PV and left atrium (LA) induced by tachypacing and isoproterenol. A Western blot analysis showed reduced expression of G protein-coupled receptor kinase 2 (GRK2) in the LA of the SD rats. Chronic partial SD impairs LV function, promotes AF genesis, and increases PV and LA arrhythmogenesis, potentially attributed to sympathetic overactivity and reduced GRK2 expression. Targeting GRK2 signaling may offer promising therapeutic avenues for managing chronic partial SD-induced AF. Future investigations are mandatory to investigate the dose-response relationship between SD and AF genesis.

Expiratory Venous Volume and Arterial Tortuosity are Associated with Disease Severity and Mortality Risk in Patients with COPD: Results from COSYCONET.

Purpose: The aim of this study was to evaluate the association between computed tomography (CT) quantitative pulmonary vessel morphology and lung function, disease severity, and mortality risk in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Participants of the prospective nationwide COSYCONET cohort study with paired inspiratory-expiratory CT were included. Fully automatic software, developed in-house, segmented arterial and venous pulmonary vessels and quantified volume and tortuosity on inspiratory and expiratory scans. The association between vessel volume normalised to lung volume and tortuosity versus lung function (forced expiratory volume in 1 sec [FEV1]), air trapping (residual volume to total lung capacity ratio [RV/TLC]), transfer factor for carbon monoxide (TLCO), disease severity in terms of Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D, and mortality were analysed by linear, logistic or Cox proportional hazard regression. Results: Complete data were available from 138 patients (39% female, mean age 65 years). FEV1, RV/TLC and TLCO, all as % predicted, were significantly (p < 0.05 each) associated with expiratory vessel characteristics, predominantly venous volume and arterial tortuosity. Associations with inspiratory vessel characteristics were absent or negligible. The patterns were similar for relationships between GOLD D and mortality with vessel characteristics. Expiratory venous volume was an independent predictor of mortality, in addition to FEV1. Conclusion: By using automated software in patients with COPD, clinically relevant information on pulmonary vasculature can be extracted from expiratory CT scans (although not inspiratory scans); in particular, expiratory pulmonary venous volume predicted mortality. Trial Registration: NCT01245933.