Progression of Atrial Fibrillation after Cryoablation or Drug Therapy.

BACKGROUND: Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation. METHODS: We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilization, and safety were collected. RESULTS: A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group. CONCLUSIONS: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation.

BACKGROUND: Guidelines recommend a trial of one or more antiarrhythmic drugs before catheter ablation is considered in patients with atrial fibrillation. However, first-line ablation may be more effective in maintaining sinus rhythm. METHODS: We randomly assigned 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation to undergo catheter ablation with a cryothermy balloon or to receive antiarrhythmic drug therapy for initial rhythm control. All the patients received an implantable cardiac monitoring device to detect atrial tachyarrhythmia. The follow-up period was 12 months. The primary end point was the first documented recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. The secondary end points included freedom from symptomatic arrhythmia, the atrial fibrillation burden, and quality of life. RESULTS: At 1 year, a recurrence of atrial tachyarrhythmia had occurred in 66 of 154 patients (42.9%) assigned to undergo ablation and in 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66; P<0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received antiarrhythmic drugs (hazard ratio, 0.39; 95% CI, 0.22 to 0.68). The median percentage of time in atrial fibrillation was 0% (interquartile range, 0 to 0.08) with ablation and 0.13% (interquartile range, 0 to 1.60) with antiarrhythmic drugs. Serious adverse events occurred in 5 patients (3.2%) who underwent ablation and in 6 patients (4.0%) who received antiarrhythmic drugs. CONCLUSIONS: Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Direct evidence gap on fixed versus adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta-analysis.

OBJECTIVES: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy. METHODS: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy. RESULTS: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses. CONCLUSIONS: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future. REGISTRATION: The study protocol was registered in PROSPERO (CRD42019120905).

Atrial Fibrillation Detected After Stroke and Transient Ischemic Attack: A Novel Clinical Concept Challenging Current Views.

Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (<30 seconds) AF paroxysms, and is more frequently associated with insular brain infarction. These distinctive features of AFDAS may explain its recently observed lower associated risk of stroke than known atrial fibrillation. We present an updated ad-hoc meta-analysis of randomized clinical trials in which the association between prolonged cardiac monitoring and reduced risk of ischemic stroke was nonsignificant (incidence rate ratio, 0.90 [95% CI, 0.71-1.15]). These findings highlight that larger and sufficiently powered randomized controlled trials of prolonged cardiac monitoring assessing the risk of stroke recurrence are needed. Meanwhile, we call for further research on AFDAS and stroke recurrence, and a tailored approach when using prolonged cardiac monitoring after ischemic stroke or transient ischemic attack, focusing on patients at higher risk of AFDAS and, more importantly, at higher risk of cardiac embolism.

Augmented wide area circumferential catheter ablation for reduction of atrial fibrillation recurrence (AWARE) trial: Design and rationale.

BACKGROUND: Recurrence of atrial fibrillation (AF) after a pulmonary vein isolation procedure is often due to electrical reconnection of the pulmonary veins. Repeat ablation procedures may improve freedom from AF but are associated with increased risks and health care costs. A novel ablation strategy in which patients receive "augmented" ablation lesions has the potential to reduce the risk of AF recurrence. OBJECTIVE: The Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence (AWARE) Trial was designed to evaluate whether an augmented wide-area circumferential antral (WACA) ablation strategy will result in fewer atrial arrhythmia recurrences in patients with symptomatic paroxysmal AF, compared with a conventional WACA strategy. METHODS/DESIGN: The AWARE trial was a multicenter, prospective, randomized, open, blinded endpoint trial that has completed recruitment (ClinicalTrials.gov NCT02150902). Patients were randomly assigned (1:1) to either the control arm (single WACAlesion set) or the interventional arm (augmented- double WACA lesion set performed after the initial WACA). The primary outcome was atrial tachyarrhythmia (AA; atrial tachycardia [AT], atrial flutter [AFl] or AF) recurrence between days 91 and 365 post catheter ablation. Patient follow-up included 14-day continuous ambulatory ECG monitoring at 3, 6, and 12 months after catheter ablation. Three questionnaires were administered during the trial- the EuroQuol-5D (EQ-5D) quality of life scale, the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale, and a patient satisfaction scale. DISCUSSION: The AWARE trial was designed to evaluate whether a novel approach to catheter ablation reduced the risk of AA recurrence in patients with symptomatic paroxysmal AF.

Cardioneuroablation for vasovagal syncope and atrioventricular block: A step-by-step guide.

Catheter-based cardioneuroablation is increasingly being utilized to improve outcomes in patients with vasovagal syncope and atrioventricular block due to vagal hyperactivity. There is now increasing convergence among enthusiasts on its various aspects, including patient selection, technical steps, and procedural end-points. This pragmatic review aims to take the reader through a step-by-step approach to cardioneuroablation: we begin with a brief overview of the anatomy of intrinsic cardiac autonomic nervous system, before focusing on the indications, preprocedure and postprocedure management, necessary equipment, and its potential limitations.

Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial.

BACKGROUND: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. OBJECTIVE: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481). SETTING: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. PATIENTS: Patients with recurrent vasovagal syncope and no serious comorbid conditions. INTERVENTION: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. MEASUREMENTS: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. RESULTS: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. LIMITATION: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. CONCLUSION: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden. PRIMARY FUNDING SOURCE: The Canadian Institutes of Health Research.

Effect of Nanopore Geometry in the Conformation and Vibrational Dynamics of a Highly Confined Molecular Glass.

The effect of nanoporous confinement on the glass transition temperature (Tg) strongly depends on the type of porous media. Here, we study the molecular origins of this effect in a molecular glass, N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD), highly confined in concave and convex geometries. When confined in controlled pore glass (CPG) with convex pores, TPD's vibrational spectra remained unchanged and two Tg's were observed, consistent with previous studies. In contrast, when confined in silica nanoparticle packings with concave pores, the vibrational peaks were shifted due to more planar conformations and Tg increased, as the pore size was decreased. The strong Tg increases in concave pores indicate significantly slower relaxation dynamics compared to CPG. Given TPD's weak interaction with silica, these effects are entropic in nature and are due to conformational changes at molecular level. The results highlight the role of intramolecular degrees of freedom in the glass transition, which have not been extensively explored.

Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy.

Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy.

Periprocedural anticoagulation in the uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation (ELIMINATE-AF) trial.

AIMS: This post hoc analysis of ELIMINATE-AF evaluated requirements of unfractionated heparin (UFH) and procedure-related bleeding in atrial fibrillation (AF) patients undergoing ablation with uninterrupted edoxaban or vitamin K antagonist (VKA) therapy. METHODS AND RESULTS: Patients were randomized 2:1 to once-daily edoxaban 60 mg (or dose-reduced 30 mg) or dose-adjusted VKA (target international normalized ratio: 2.0-3.0). Uninterrupted anticoagulation was mandated for 21-28 days' pre-ablation and 90 days' post-ablation. During ablation, UFH administration targeted an activated clotting time (ACT) of 300-400 s. Periprocedural bleeding was differentiated between procedure-related (bleeding at puncture side, cardiac tamponade) and unrelated events. Of 614 randomized patients, 553 received study drug and underwent catheter ablation (edoxaban n = 375; VKA n = 178). The median (Q1-Q3) time from last dose to ablation procedure was 14.8 (13.3-16.5) vs. 16.5 (14.8-19.5) h (edoxaban vs. VKA group, respectively). Mean ACT (SD) ≥300 s was observed in 52% edoxaban- vs. 76% VKA-treated patients, despite a higher mean (SD) UFH dose in the edoxaban vs. VKA group [14 261 (6397) IU vs. 11 473 (4300) IU; exploratory P-value < 0.0001]. In the edoxaban group, 13 patients (3.5%) had procedure-related bleeds of whom 9 had received an UFH dose above the median (13 000 IU). In the VKA arm, 7 patients (3.9%) had procedure-related bleeds of whom 3 had received an UFH dose above the median (10 225 IU). CONCLUSION: The rate of procedure-related major/clinically relevant non-major bleeding did not differ between the treatment arms despite higher doses of UFH used with edoxaban vs. VKA to achieve a target ACT during AF ablation.

Survival after heart transplantation for Chagas cardiomyopathy using a conventional protocol: A 10-year experience in a single center.

BACKGROUND: Heart transplant (HT) remains the most frequently indicated therapy for patients with end-stage heart failure that improves prognosis in Chagas cardiomyopathy (CCM). However, the lack of benznidazole therapy and availability of RT-PCR follow-up in many centers is a major limitation to perform this life-saving intervention, as there are concerns related with the risk of reactivation. We aimed to describe the outcomes of a cohort of patients with CCM who underwent HT using a conventional protocol with mycophenolate mofetil, without benznidazole prophylaxis or RT-PCR follow-up. METHODS: Retrospective cohort study. Between 2008 and 2018, 43 patients with CCM underwent HT. A descriptive analysis to characterize outcomes as rejection, infectious and neoplastic complications and a survival analysis was carried out. RESULTS: Median of follow-up was 4.3 (IR 4.28) years. Survival at 1 month, 1 year, and 5 years was 95%, 85%, and 75%, respectively, infections being the main cause of death (60%). Reactivations occurred in only three patients (7.34%) and were not related to mortality. CONCLUSION: This cohort showed a favorable survival and a low reactivation rate without an impact on mortality. Our results suggest that performing HT in patients with CCM following conventional guidelines and recommendations for other etiologies is a safe approach.

Croton lechleri Extracts as Green Corrosion Inhibitors of Admiralty Brass in Hydrochloric Acid.

Croton lechleri, commonly known as Dragon's blood, is a tree cultivated in the northwest Amazon rainforest of Ecuador and Peru. This tree produces a deep red latex which is composed of different natural products such as phenolic compounds, alkaloids, and others. The chemical structures of these natural products found in C. lechleri latex are promising corrosion inhibitors of admiralty brass (AB), due to the number of heteroatoms and π structures. In this work, three different extracts of C. lechleri latex were obtained, characterized phytochemically, and employed as novel green corrosion inhibitors of AB. The corrosion inhibition efficiency (IE%) was determined in an aqueous 0.5 M HCl solution by potentiodynamic polarization (Tafel plots) and electrochemical impedance spectroscopy, measuring current density and charge transfer resistance, respectively. In addition, surface characterization of AB was performed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy techniques. Chloroform alkaloid-rich extracts resulted in IE% of 57% at 50 ppm, attributed to the formation of a layer of organic compounds on the AB surface that hindered the dezincification process. The formulation of corrosion inhibitors from C. lechleri latex allows for the valorization of non-edible natural sources and the diversification of the offer of green corrosion inhibitors for the chemical treatment of heat exchangers.

Circulating Trypanosoma cruzi load and major cardiovascular outcomes in patients with chronic Chagas cardiomyopathy: a prospective cohort study.

OBJECTIVES: To analyse the effect of parasite load assessed by quantitative reverse transcription PCR (RT-qPCR) in serum on the prognosis of patients with chronic Chagas cardiomyopathy (CCM) after a 2-year follow-up. METHODS: Prospective cohort study conducted between 2015 and 2017. One hundred patients with CCM were included. Basal parasitaemia levels of Trypanosoma cruzi (T. cruzi) were measured using a quantitative polymerase chain reaction (qPCR) test. The primary composite outcome (CO) was all-cause mortality, cardiac transplantation and implantation of a left ventricular assist device. Secondary outcomes were the baseline levels of serum biomarkers and echocardiographic variables. RESULTS: After a 2 years of follow-up, the primary CO rate was 16%. A positive qPCR was not associated with a higher risk of the CO. However, when parasitaemia was evaluated by comparing tertiles (tertile 1: undetectable parasitaemia, tertile 2: low parasitaemia and tertile 3: high parasitaemia), a higher risk of the CO (HR 3.66; 95% CI 1.11-12.21) was evidenced in tertile 2. Moreover, patients in tertile 2 had significantly higher levels of high-sensitivity troponin T and cystatin C and more frequently exhibited an ejection fraction <50%. CONCLUSION: Low parasitaemia was associated with severity markers of myocardial injury and a higher risk of the composite outcome when compared with undetectable parasitaemia. This finding could be hypothetically explained by a more vigorous immune response in patients with low parasitaemia that could decrease T. cruzi load more efficiently, but be associated with increased myocardial damage. Additional studies with a larger number of patients and cytokine measurement are required to support this hypothesis.

OBJECTIFS: Analyser l'effet de la charge parasitaire évaluée par PCR quantitative de transcription inverse (RT-qPCR) dans le sérum sur le pronostic des patients atteints de cardiomyopathie chronique de Chagas (CCM) après un suivi de deux ans. MÉTHODES: Etude de cohorte prospective menée entre 2015 et 2017. Une centaine de patients atteints de CCM ont été inclus. Les niveaux de parasitémie basale de Trypanosoma cruzi (T. cruzi) ont été mesurés en utilisant un test de réaction en chaîne de la polymérase quantitative (qPCR). Le principal résultat composite (RC) était la mortalité toutes causes, la transplantation cardiaque et l'implantation d'un dispositif d'assistance ventriculaire gauche. Les critères secondaires étaient les niveaux de base des biomarqueurs sériques et des variables échocardiographiques. RÉSULTATS: Après 2 ans de suivi, le taux de RC primaire était de 16%. Une qPCR positive n'était pas associée à un risque plus élevé de RC. Cependant, lorsque la parasitémie était évaluée en comparant les tertiles (tertile 1: parasitémie indétectable, tertile 2: parasitémie faible et tertile 3: parasitémie élevée), un risque plus élevé de RC (HR: 3,66; IC95%: 1,11-12,21) a été mis en évidence dans le tertile 2. De plus, les patients du tertile 2 avaient des niveaux significativement plus élevés de troponine T et de cystatine-C à haute sensibilité et présentaient plus fréquemment une fraction d'éjection <50%. CONCLUSION: Une faible parasitémie était associée à des marqueurs de sévérité des lésions myocardiques et à un risque plus élevé de résultat composite par rapport à une parasitémie indétectable. Cette découverte pourrait être hypothétiquement expliquée par une réponse immunitaire plus vigoureuse chez les patients présentant une faible parasitémie qui pourrait diminuer la charge de T. cruzi plus efficacement mais être associée à une augmentation des lésions myocardiques. Des études supplémentaires avec un plus grand nombre de patients et une mesure des cytokines sont nécessaires pour étayer cette hypothèse.

Chagas heart disease: A contemporary review.

Chagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage before the development of symptoms. The prognosis of patients with Chagasic cardiomyopathy remains poor and life-threatening ventricular arrhythmias can occur at an early stage. Treatment of chronic Chagas cardiomyopathy is challenging with a great need for more studies in the field.

Relationship between quality of life and burden of recurrent atrial fibrillation following ablation: CAPCOST multicentre cohort study.

AIMS: Atrial fibrillation (AF) significantly impairs patients' quality of life (QOL). We performed this study to investigate the effect of AF-ablation success and atrial fibrillation burden (AFB) on QOL measures. METHODS AND RESULTS: Overall, 230 patients with paroxysmal AF refractory to antiarrhythmic drugs were enrolled and underwent ablation in a multicentre, prospective cohort. Electrocardiogram, 48-h Holter, Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF), short form-12 (SF-12), and Atrial Fibrillation Effect on Quality of life (AFEQT) scales were used to assess patients. Atrial fibrillation burden was defined as total duration of AF during the month prior to each visit (h/month). The change in AFB was calculated as the difference between the month prior to the 12-month post-ablation and the baseline pre-ablation. The Minimal Clinically Important Difference (MCID) was considered as a 19-point change for AFEQT and 3-5-point change for SF-12 scores. There was significant rise in the AFEQT and SF12 and decrease in CCS-SAF score post-AF ablation; however, the magnitude of these changes was greater in patients without AF recurrence (P < 0.05). The QOL score that best differentiated patients with and without recurrence was AFEQT, while, CCS-SAF was the most specific score. Patients with AFB decrease >19 h/month had significantly greater change in QOL scores. Atrial fibrillation burden < 24 h/month at 12-months post-ablation was associated with significant changes in QOL and CCS-SAF when adjusting for baseline scores and other covariates. These changes were consistent with the MCID of these measures. CONCLUSION: Patients experience significant improvements in QOL post-ablation, which correlate with a decrease in AFB despite ongoing brief recurrences of AF. CLINICAL TRIAL REGISTRATION: NCT01562912. https://www.clinicaltrials.gov/ct2/show/NCT01562912? term=capcost&rank=1.

Impact of dual-chamber pacing with closed loop stimulation on quality of life in patients with recurrent reflex vasovagal syncope: results of the SPAIN study.

AIMS: Reflex vasovagal syncope (VVS) is the most common cause of syncope and patients with recurrent episodes may severely impair quality of life (QoL). This pre-specified analysis evaluated whether the clinically significant reduction in syncope burden demonstrated by dual-chamber pacing with closed loop stimulation (DDD-CLS) reported in the SPAIN trial translates into improved QoL. METHODS AND RESULTS: Patients aged ≥40 years with ≥5 VVS episodes and cardioinhibitory response induced by head-up tilt testing were included. Patients were randomized 1:1 to active DDD-CLS pacing algorithm for 12 months followed by sham DDI mode for the remaining 12 months (Group A) or vice versa (Group B). QoL was assessed using the Short Form-36 (SF-36) health survey, Physical Component Score (PCS), and Mental Component Score (MCS) before randomization (baseline) and at 12- and 24-month follow-up. Fifty-four patients were enrolled from 11 participating centres. No significant carryover effect was detected for any variable, and the only period effect was observed in the vitality subdomain (P = 0.033). Mean SF-36 scores were higher in the DDD-CLS group vs. the DDI group for the eight subdomains and significantly different in physical role, bodily pain, and vitality (P < 0.05). The analysis of component summary scores indicated that DDD-CLS benefited both mental and physical components with significant differences in PCS when compared with the DDI group. CONCLUSION: Dual-chamber pacing with closed loop stimulation determined a significant and clinically relevant improvement in QoL across both mental and physical components in patients with recurrent VVS. REGISTRATION: Closed Loop Stimulation for Neuromediated Syncope (SPAIN Study); NCT01621464.

Echocardiographic parameters, speckle tracking, and brain natriuretic peptide levels as indicators of progression of indeterminate stage to Chagas cardiomyopathy.

BACKGROUND: Chronic Chagas cardiomyopathy (CCM) is characterized by a unique type of cardiac involvement. Few studies have characterized echocardiographic (Echo) transitions from the indeterminate Chagas disease (ChD) form to CCM. The objective of this study was to identify the best cutoffs in multiple Echo parameters, speckle tracking, and N-terminal pro B-type natriuretic peptide (NT-proBNP) to distinguish patients without CCM (stage A) vs patients with myocardial involvement (stages B, C, or D). METHODS: Cross-sectional study conducted in 273 consecutive patients with different CCM stages. Echo parameters, NT-proBNP, and other clinical variables were measured. Logistic regression models (dichotomized in stage A versus B, C, and D) adjusted for age, sex, body mass index, and NT-proBNP were performed. RESULTS: Left ventricular global longitudinal strain (LV-GLS), mitral flow E velocity, LV mass index, and NT-proBNP identified early changes that differentiated stages A vs B, C, and D. The LV-GLS with a cutoff -20.5% showed the highest performance (AUC 92.99%; accuracy 84.56% and negative predictive value (NPV) 88.82%), which improved when it was additionally adjusted by NT-proBNP with a cutoff -20.0% (AUC 94.30%; accuracy 88.42% and NPV 93.55%). CONCLUSIONS: Our findings suggest that Echo parameters and NT-proBNP may be used as diagnostic variables in detecting the onset of myocardial alterations in patients with the indeterminate stage of ChD. LV-GLS was the more accurate measurement regarding stage A differentiation from the stages B, C, and D. Prospective longitudinal studies are needed to validate these findings.

Head-up tilt test diagnostic yield in syncope diagnosis.

BACKGROUND: The European Syncope Guidelines (ESG) recommend the use of Head-up tilt test (HUT) in case of suspicion of vasovagal syncope (VVS) or orthostatic hypotensive syncope (OHS) after an adequate initial inconclusive evaluation. We report a single center experience in the scenario of suspected VVS or OHS, who underwent HUT in patients referred to a Syncope Clinic after ruling out high-risk causes. METHODS: We prospectively and consecutively included all syncopal patients that were referred for HUT, by their attending physician after performing a series of diagnostic tests to rule out cardiac etiology. The clinical history and diagnostic tests performed were reviewed prior to HUT. Patients were pre-classified according to the recommendations from the ESG as; VVS, OHS or Syncope of Unknown Etiology (SUE). RESULTS: We studied 1058 patients, 558 (52.7%) males, mean age 46.5 ±â€¯20.1 yr. There were no gender differences in age, risk factors, previous heart diseases, ECG findings or number of previous tests. Based on the ESG criteria a significant number of diagnostic tests were probably unnecessarily performed. HUT was positive in 609 patients (57.5%). The rate of positive HUT according to pre-classification was significantly different among groups: 60% VVS, 46.1% OHS and 54.3% SUE (p = 0.037). Combining ESG recommendations and HUT results of the 1058 resulted in 762 (72%) diagnosed as VVS, 89 (8.4%) as OHS and 207 (19.5%) as SUE. CONCLUSIONS: Appropriate application of ESG recommendations combined with HUT, identified 81% of patients with non-cardiogenic syncope, potentially avoiding a significant number of unnecessary diagnostic tests.

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

AIMS: Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. METHODS AND RESULTS: The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). CONCLUSION: Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.