New insights into the clinical signs of supraventricular tachycardia: The "sign of lace-tying".

BACKGROUND: Supraventricular tachycardias (SVT) are a common arrhythmia therefore an accurate diagnosis is of clinical importance. Although an ECG performed during tachycardia greatly aids diagnosis, patient history and predisposing factors also improve diagnostic accuracy. METHODS: This prospective study included 100 consecutive patients undergoing electrophysiological study for SVT with the aim to reassess their clinical characteristics and describe frequent predisposing factors, such as the "sign of lace-tying" that to our knowledge has not previously been reported. Each patient completed an extensive questionnaire (70 questions) during their hospital stay. RESULTS: Our series comprised: 67% of patients with atrioventricular nodal reentrant tachycardia (AVNRT); 24% with an accessory pathway; and 9% presented atrial tachycardia. Half of the population were male and 29% of the cohort presented hypertension. Syncope during tachycardia appeared in 15% of patients, dizziness in 52% and thoracic pain in 59%. We encountered a predisposing risk factor for SVT in 53% of cases; with 32% exhibiting an anteflexion of the trunk termed the "sign of lace-tying." Data also showed that younger patients tended to present AVRT and regular pounding in the neck appeared only in patients with AVNRT. CONCLUSIONS: Overall, our study has highlighted the importance of considering clinical signs and patient characteristics both before and during SVT for the precise diagnosis of paroxysmal SVT. Furthermore, 32% of patients presented the "sign of lace-tying" or body position change before SVT, implying a diagnosis of SVT.

Integrity of the Ganglionated Plexi Is Essential to Parasympathetic Innervation of the Atrioventricular Node by the Right Vagus Nerve.

INTRODUCTION: Radiofrequency isolation of pulmonary vein can be accompanied by transient sinus bradycardia or atrioventricular nodal (AVN) block, suggesting an influence on vagal cardiac innervation. However, the importance of the atrial fat pads in relation with the vagal innervation of AVN in humans remains largely unknown. The aim of this study was to evaluate the role of ganglionated plexi (GP) in the innervation of the AVN by the right vagus nerve. METHODS AND RESULTS: Direct epicardial high-frequency stimulation (HFS) of the GP (20 patients) and the right vagus nerve (10 patients) was performed before and after fat pad exclusion or destruction in 20 patients undergoing thoracoscopic epicardial ablation for the treatment of persistent AF. Asystole longer than 3 seconds or acute R-R prolongation over 25% was considered as a positive response to HFS. Prior to the ablation, positive responses to HFS were detected in 3 GPs in 7 patients (35%), 2 GPs in 5 patients (25%), and one GP in 8 patients (40%). After exclusion of the fat pads, all patients had a negative response to HFS. All the patients who exhibited a positive response to right vagus nerve stimulation (n = 10) demonstrated negative responses after the ablation. CONCLUSION: The integrity of the GP is essential for the right vagus nerve to exert physiological effects of on AVN in humans.

Regional differences in referral, procedures, and outcome after ablation for atrial fibrillation in Europe: a report from the Atrial Fibrillation Ablation Pilot Registry of the European Society of Cardiology.

AIMS: Ablation is an effective treatment of symptomatic and drug refractory atrial fibrillation (AF). Using data from the European AF Ablation Pilot Registry comprising 1410 patients from 10 European countries, we prospectively investigated regional differences in AF ablation regarding patient selection, ablation strategy, and outcome. METHODS AND RESULTS: Countries were divided into three regions: South (Greece, Italy, Spain), East (Czech Republic, Poland), and West/North (Belgium, Denmark, France, Germany, and the Netherlands). One-year success was defined as patient survival free from atrial arrhythmia, with or without antiarrhythmic drugs (AAD). In all regions, patients were symptomatic and treated extensively with beta-blockers and AAD pre-ablation. Patients in East had more co-morbidity, increased thromboembolic risk, were more likely to have paroxysmal AF, and they underwent more left atrial linear ablations. Adverse events remained within expected levels, albeit with a significantly higher reporting of adverse cardiovascular events in the West/North (4.7 vs. 1.4 and 1.5% in South and East, P = 0.0032). There was no significant difference in peripheral/vascular, neurological, pulmonary, gastrointestinal, or general adverse events. The 1-year success rate after ablation differed non-statistically between regions ranging from 69.1 to 74.7%. A second ablation was performed in 23.2% in West/North compared with 10.5 and 16.5% in South and East. The proportion of patients still on AADs was highest in the South region (51.6 vs. 42.3 and 38.8% in East and West/North). CONCLUSION: This study with all-comer patients shows that patient selection for ablation follows current guidelines but reveals significant differences regarding co-morbidity, medication, and ablation strategy. Despite this, 1-year outcomes are without significant differences and in line with previously published clinical trials.

Method, safety, and outcomes of persistent AF ablation without a circular mapping catheter: 3 years experience of a Belgian Tertiary Centre.

BACKGROUND: We aimed to share our methods and experience of persistent AF ablation without a circular mapping catheter (CMC), thereby avoiding femoral venous and transseptal punctures, decreasing the cost of the procedure, and possibly reducing the duration of the procedure and fluoroscopy time. METHODS: We report our experience with 261 persistent AF ablations performed without a CMC over the past 3 years. RESULTS: The procedures were performed with no apparent loss of efficacy or safety. Freedom from recurrence was defined as a 1-year absence of AF/atrial flutter (AFL) episodes >30 s, beyond the 3-month blanking period. At 1 year, 72% of the patients were free from arrythmias. CONCLUSIONS: Persistent AF ablation is feasible without a CMC, reducing the need for venous and transseptal punctures and the cost of the procedure. We suggest that prospective studies should aim to characterise the reduction in procedure and fluoroscopy times as a result of this technique.

Impact of Pre-Transplant Left Ventricular Diastolic Pressure on Primary Graft Dysfunction after Lung Transplantation: A Narrative Review.

Lung transplantation (LT) constitutes the last therapeutic option for selected patients with end-stage respiratory disease. Primary graft dysfunction (PGD) is a form of severe lung injury, occurring in the first 72 h following LT and constitutes the most common cause of early death after LT. The presence of pulmonary hypertension (PH) has been reported to favor PGD development, with a negative impact on patients' outcomes while complicating medical management. Although several studies have suggested a potential association between pre-LT left ventricular diastolic dysfunction (LVDD) and PGD occurrence, the underlying mechanisms of such an association remain elusive. Importantly, the heterogeneity of the study protocols and the various inclusion criteria used to define the diastolic dysfunction in those patients prevents solid conclusions from being drawn. In this review, we aim at summarizing PGD mechanisms, risk factors, and diagnostic criteria, with a further focus on the interplay between LVDD and PGD development. Finally, we explore the predictive value of several diastolic dysfunction diagnostic parameters to predict PGD occurrence and severity.

Emerging Trends in Left Ventricular Thrombus: A Comprehensive Review of Non-Ischemic and Ischemic Cardiopathies, Including Eosinophilic Myocarditis, Chagas Cardiomyopathy, Amyloidosis, and Innovative Anticoagulant Approaches.

This comprehensive review explores the intricate aspects of left ventricular thrombus (LVT), a potential complication in both ischemic and non-ischemic cardiomyopathies. It provides a thorough understanding of left ventricular thrombus, revealing its uncommon incidence in the general population (7 cases per 10,000 patients), predominantly linked to ischemic heart diseases (ICMs) at an 80% prevalence rate. Diagnostic tools, notably transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR), demonstrate varying sensitivity but remain indispensable in specific clinical contexts related to LVT as non-invasive diagnostic modalities. A detailed comparison between ICM patients and those with non-ischemic cardiomyopathy (NICM) who have left ventricular thrombus reveals subtle distinctions with significant clinical implications. This analysis underscores the importance of these imaging techniques in distinguishing between the two conditions. Additionally, we explored the occurrence of LVT in specific non-ischemic cardiomyopathies, including Takotsubo syndrome, hypertrophic cardiomyopathy, eosinophilic myocarditis, Chagas disease, cardiac amyloidosis, and several other conditions. The article further delves into anticoagulation strategies, thoroughly examining their impact on LVT regression and patient outcomes. Pharmacological interventions, with a focus on direct oral anticoagulants, emerge as promising alternatives; however, there is insufficient information on their efficiency and safety, especially in NICM population. In conclusion, this review highlights the complex nature of LVT, incorporating a range of etiopathogenic factors, diagnostic complexities, and evolving therapeutic approaches. It emphasizes the pressing need for ongoing research in this field.

Distinct Substrates of Idiopathic Ventricular Fibrillation Revealed by Arrhythmia Characteristics on Implantable Cardioverter-Defibrillator.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts. OBJECTIVE: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates. METHODS: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates. RESULTS: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF. CONCLUSIONS: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications.

Predictive value of thromboembolic risk scores before an atrial fibrillation ablation procedure.

INTRODUCTION: It is not clear whether transesophageal echocardiography (TEE) should be performed prior to a planned atrial fibrillation (AF) ablation in all patients. METHODS AND RESULTS: The objectives of this study were to determine in 681 consecutive patients: (i) the relationship between the CHADS2 and CHA2DS2-VASc scores, the presence of a thrombogenic milieu and left atrial (LA) volume; (ii) the need for TEE in patients with low and intermediate thromboembolic risk assessed; and (iii) the predictive accuracy of the these 2 scores for the presence of thrombi in the LA/LAA (LA appendage) before a planned AF ablation. The prevalence of thrombi was 1%. All patients with thrombi had LA dilatation, a CHADS2 score ≥ 1 and a CHA2DS2-VASc score ≥ 2. CHADS2 or CHA2DS2-VASc scores <2 had an almost maximal negative predictive capability of excluding the presence of a thrombus (99.8% and 100%, respectively; 95% CI: 99-100). A CHADS2 score ≥ 2 had a sensitivity and specificity of 86% (95% CI: 42-100) and 82% (95% CI: 79-85), respectively, to predict the presence of a thrombus in the LA/LAA, while a CHA2DS2-VASc score ≥ 2 had a sensitivity and specificity of 100% (95% CI: 59-100) and 67% (95% CI: 63-70). The area under the curve for CHADS2 and CHA2DS2-VASc scores ≥ 2 was 0.928 (95% CI: 0.906-0.946) and 0.933 (95% CI: 0.912-0.951), respectively. CONCLUSION: Not all patients undergoing planned endocardial pulmonary vein isolation need preprocedural TEE. Both scores <2 had an almost maximal negative predictive capability of excluding the presence of a thrombus in the LA/LAA.

Unmasking Pandemic Echoes: An In-Depth Review of Long COVID's Unabated Cardiovascular Consequences beyond 2020.

At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.

Intravenous adenosine to predict conduction recurrence in cavotricuspid isthmus early after ablation of typical atrial flutter: myth or reality?

INTRODUCTION: Early recovery of conduction (ER) after cavotricuspid isthmus (CTI) ablation for typical atrial flutter (AFl) occurs in approximately 10% of the patients. If not recognized, ER might lead to AFl recurrences. In this study, we hypothesized that intravenous adenosine (iADO) can be used to predict ER in the CTI immediately after RF ablation and distinguish functional block from the complete destruction of the CTI myocardium. METHODS: We prospectively included 68 consecutive patients (age: 65 ± 14 years; male: 78%) referred in our centers for AFl ablation. Immediately after bidirectional isthmus block validation, a bolus of iADO was given during continuous pacing from the proximal coronary sinus. Patients with functional block revealed under iADO (iADO+) and those without (iADO-) were subsequently observed for a 30-minute waiting period (ER-) or until sustained recovery of the conduction through the CTI (ER+). RESULTS: Seven patients presented a persistent recovery (ER+, 10.3%, mean time to recovery: 14 ± 9 minutes). None of them presented even a transient resumption of conduction under iADO (iADO+: 0). With univariate analysis, we identified a heavy patient weight (>95 kg) as a predictor of ER (sensitivity: 71%). CONCLUSIONS: Adenosine does not predict early recovery in the CTI after linear ablation for atrial flutter. We found that a patient weight over 95 kg predicted early recovery of conduction through the CTI with a sensitivity of 71%.

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?

Most patients present for catheter ablation of atrial fibrillation (CAAF) with residual or full effect of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). In daily practice, it has been observed that the activated clotting time (ACT) was actually poorly sensitive to the effect of DOACs and that patients on DOACs required more unfractionated heparin (UFH) to achieve the ACT target of 300 s during the procedure, leading some authors to worry about potential overdosing. Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during CAAF regardless of the residual effect of DOACs. During CAAF, thrombosis is promoted mainly by the presence of thrombogenic sheaths and catheters in the bloodstream. Preclinical data suggest that only high doses of DOACs are able to mitigate catheter-induced thrombin generation, whereas low dose UFH already do so. In addition, the effect of UFH seems to be lower in patients on DOACs, compared to patients on VKAs, explaining part of the differences observed in heparin requirements. Clinical studies could not identify increased bleeding risk in patients on DOACs compared to those on VKAs despite similar efficacy during CAAF procedures. Moreover, targeting a lower ACT was associated with an increased periprocedural thrombotic risk for both DOAC and VKA patients. Therefore, the low sensitivity of the ACT to the residual effect of DOACs should not be a major concern in its use in the interventional cardiology laboratory.

Mitral isthmus block in a case of persistent left superior vena cava.

Persistent left superior vena cava (LSVC), an uncommon venous anomaly, could be an arrhythmogenic source of atrial fibrillation. Multiple electrical connections were reported between the LSVC and the left atrium, which may negatively impact the achievement of conduction block during linear ablation of left mitral isthmus. We describe a case with perimitral atrial flutter (AFL) in a patient with isolated LSVC. AFL was successfully treated and complete perimitral conduction block was achieved following a lengthy epicardial radiofrequency application.

Initial results of efficacy of left linear ablation using a novel simultaneous multielectrode ablation catheter.

INTRODUCTION: Creating complete linear block with point-by-point ablation is challenging in the left atrium (LA). The purpose of this study was to evaluate the efficacy of LA linear ablation using a hexapolar linear multielectrode mapping/ablation catheter. METHODS AND RESULTS: Seventeen patients (age 57 ± 10, 14 male, 6 paroxysmal AF (PAF)) were studied and underwent linear ablation at the mitral isthmus (MI) and LA roof. Ablation was performed with 90 second, 60 °C applications of duty-cycled bipolar/unipolar radiofrequency in a 1:1 ratio simultaneously at all selected electrode pairs. The result could not be evaluated in 2 patients because AF persisted despite cardioversion. Roof line block was confirmed in 9 of 15 (60%) patients. The mean number of applications and the procedural time with and without block was 5.4 ± 2.4 and 4.5 ± 2.2 applications, and 15 ± 8 and 13 ± 7 minutes. MI block was confirmed in 4 of 15 (27%) patients. The mean number of RF applications with and without block was 5.3 ± 2.2 and 9.9 ± 4.4 applications, and the procedural time was 20 ± 9 and 27 ± 10 minutes, respectively. For patients with underlying persistent AF, power was lower than those with PAF but improved when ablation was performed in sinus rhythm. Char was observed in 2 cases; however, no procedure-related complications were observed. CONCLUSIONS: In our initial experience, a linear multielectrode catheter using duty-cycled bipolar and unipolar RF energy was inferior to conventional single point irrigated ablation in achieving LA linear block. However, successful linear block was obtained within a short period of time, when it was achieved.

Impact of patent foramen ovale on left atrial linear lesions in the context of atrial fibrillation ablation.

INTRODUCTION: We investigated the impact of the mode of left atrial (LA) access via patent foramen ovale (PFO) versus transseptal (TS) puncture on LA linear lesions during atrial fibrillation (AF) ablation. METHODS AND RESULTS: We investigated 139 (PFO: 25) consecutive patients who underwent mitral isthmus (MI) and/or LA roof linear ablation. Technical endpoint was completeness of linear lesions and duration of radiofrequency (RF) application. During the initial procedure, complete MI and LA roof blocks were created in 13 of 19 (68%) and 14 of 17 (82%) patients in the PFO group, and in 57 of 94 (61%) and 54 of 70 (74%) patients in the TS group, respectively (P = NS). There was no significant difference in RF durations at MI (11.1 ± 8.9 and 15.1 ± 7.6 minutes, P = 0.11), and LA roof (10.1 ± 3.5 and 8.3 ± 5.0 minutes, P = 0.21) between the 2 groups. Among 28 patients who underwent repeat linear ablation, complete MI and LA roof blocks were created in 3 of 4 (75%) and 0 of 1 (0%) patients in the PFO group, and in 16 of 21 (76%) and 7 of 10 (70%) patients in the TS group, respectively (P = NS). There was no significant difference in RF durations at MI (15.3 ± 8.3 and 19.5 ± 18.3 minutes, P = 0.71), and LA roof (19.0 and 10.3 ± 5.4 minutes, P = 0.19) between the 2 groups. Clinical outcomes at 12 months were also similar. CONCLUSION: There were no significant differences in the procedural success rates, durations of RF application, 12-month clinical outcomes, and complication rates of LA linear ablation between the PFO and TS groups. Accessing the LA via a PFO is not an unfavorable approach toward LA linear ablation.

3D navigation system allows remarkable reduction in fluoroscopy use during cavo-tricuspid isthmus ablation.

PURPOSE: Typical atrial flutter (AFL) is one of the most common supraventricular arrhythmias. Its treatment mainly relies on cavo-tricuspid isthmus (CTI) ablation, which can be performed either using conventional fluoroscopy, still mainly used, or 3D navigation system to track the position of the catheter. The aim of this study is to show that the use of a 3D navigation system allows a dramatic reduction of fluoroscopy use during CTI ablation, without any loss of efficacy, time, or safety. METHODS: In this single-center study, we retrospectively compared 134 cases of CTI ablation performed for typical AFL without a 3D navigation system with 95 cases of CTI ablation performed with such a 3D system. We compared the rates of procedural success (defined as obtaining a bidirectional electrical conduction block), freedom from AFL recurrence at 1-year follow-up, procedural time and safety, and fluoroscopy use. RESULTS: Compared to conventional fluoroscopy, the use of a 3D navigation system significantly decreased the duration of fluoroscopy use (2 min 13 s ± 2 min 16 s versus 14 min 41 s ± 10 min 39 s, p < 0.0001) and dose-area products (1567.9 ± 1329.5 mGy cm2 versus 8263.3 ± 8636.6 mGy cm2, p < 0.0001). Procedure success rates, duration, and safety were not different between groups. CONCLUSIONS: The use of 3D navigation during CTI ablation substantially reduces fluoroscopy use duration, without reducing the success rates and safety or prolonging the procedure duration, as compared to conventional fluoroscopy. We therefore suggest the generalization of this navigation system.

A circular mapping catheter is not mandatory for isolating pulmonary veins during paroxysmal atrial fibrillation ablation with radiofrequency.

PURPOSE: In this study, we evaluated the feasibility, efficacy, and safety of radiofrequency ablation of paroxysmal atrial fibrillation (AF) with the use of an ablation catheter only (non-CMC group) by retrospectively comparing its procedural success and recurrence rates at 1 year to ablation performed with the help of a circular mapping catheter (CMC group). METHODS: We compared the success and recurrence rates between 226 patients and 251 patients who underwent index ablation with and without the use of CMC, respectively. RESULTS: Freedom from recurrence was defined as a 1-year absence of AF/atrial tachycardia (AT) episodes > 30 s, beyond the 3-month blanking period. There was no significant difference between the number of pulmonary vein isolations, recurrence rate of AF/AT, and the use of antiarrhythmic drugs after 1 year of ablation. The procedure and fluoroscopy times were lower in the non-CMC group compared with the CMC group (106 ± 33 vs. 125 ± 32 min, p < 0.0001; 2.2 ± 1.9 vs. 2.7 ± 2.3 min, p = 0.0002, respectively). CONCLUSIONS: Pulmonary vein isolation without the use of a CMC is feasible; moreover, the material costs, procedure time, and radiation exposure were reduced compared with the CMC group. Freedom of recurrence was similar between groups. Optimized use of 3D electro-anatomical mapping systems could reduce the radiation exposure for both the patient and physician.

Impact of different anticoagulation management strategies on outcomes in atrial fibrillation: Dutch and Belgian results from the GARFIELD-AF registry.

BACKGROUND: The uptake rate of non-vitamin K oral anticoagulants (NOAC) for the treatment of non-valvular atrial fibrillation (AF) was far lower in the Netherlands (NL) compared to Belgium (BE). Also, patients on VKA in NL were treated with a higher target international normalized ratio (INR) range of 2.5 to 3.5. OBJECTIVES: To explore the effect of these differences on thromboembolism (TE) and bleeding. METHODS: Data from the GARFIELD-AF registry was used. Patients with new-onset AF and ≥1 investigator-determined risk factor for stroke were included between 2010 and 2016. Event rates from 2 years of follow-up were used. RESULTS: In NL and BE, 1186 and 1705 patients were included, respectively. Female sex (42.3% vs 42.2%), mean age (70.7 vs 71.3 years), CHA2 DS2 -VASc (3.1 vs 3.1), and HAS-BLED score (1.4 vs 1.5) were comparable between NL and BE. At diagnosis in NL vs BE, 72.1% vs 14.6% received vitamin K antagonists (VKA) and 17.8% vs 65.5% NOACs, varying greatly across cohorts. Mean INR was 2.9 (±1.0) and 2.4 (±1.0) in NL and BE, respectively. Event rates per 100 patient-years in NL and BE, respectively, of all-cause mortality (3.38 vs 3.90; hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15), ischemic stroke/TE (0.82 vs 0.72; HR 1.14, 95% CI 0.62-2.11), and major bleeding (2.06 vs 1.54; HR 1.33, 95% CI 0.89-1.99) did not differ significantly. CONCLUSIONS: In GARFIELD-AF, despite similar characteristics, patients on anticoagulants were treated differently in NL and BE. Although the rate of major bleeding was 33% higher in NL, variations in bleeding, mortality, and TE rates were not statistically significant.

Nicotine increases chemoreflex sensitivity to hypoxia in non-smokers.

BACKGROUND: The peripheral chemoreflex contributes to cardiovascular regulation and represents the first line of defence against hypoxia. The effects of nicotine on chemoreflex regulation in non-smoking humans are unknown. METHOD: We conducted a prospective, randomized, crossover, and placebo-controlled study in 20 male non-smokers to test the hypothesis that nicotine increases chemoreflex sensitivity. The effects of two intakes of 2 mg nicotine tabs and placebo on sympathetic nerve activity to muscle circulation (muscle sympathetic nerve activity; MSNA), minute ventilation (Ve), blood pressure and heart rate were assessed during normoxia, moderate isocapnic hypoxia, hyperoxic hypercapnia and an isometric handgrip in 10 subjects. Maximal end-expiratory apnoeas were performed at baseline and at the end of the fifth minute of hypoxia. In a second experimental setting, we studied the ventilatory response to a more marked isocapnic hypoxia in 10 other volunteers. RESULTS: Mean MSNA and Ve were not modified by nicotine during the 5 min of normoxia or moderate hypoxia. In the presence of nicotine MSNA was related to oxygen desaturation (P < 0.01). The sympathoexcitatory effects of nicotine became especially evident when apnoeas achieved oxygen saturations less than 85% (511 +/- 44% increase in MSNA after the first intake, and 436 +/- 43% increase after the second intake versus 387 +/- 56% and 338 +/- 31% with placebo, respectively, P < 0.05). Nicotine also increased the ventilatory response compared with placebo when oxygen saturation decreased to less than 85% (P < 0.05). CONCLUSION: This is the first study to demonstrate that nicotine increases peripheral chemoreflex sensitivity to large reductions in arterial oxygen content in healthy non-smokers.