Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Nurse-led care after ablation of atrial fibrillation: a randomized controlled trial.

AIMS: The added value of advanced practitioner nurse (APN) care after ablation of atrial fibrillation (AF) is unknown. The present study investigates the impact of APN-led care on AF recurrence, patient knowledge, lifestyle, and patient satisfaction. METHODS AND RESULTS: Sixty-five patients undergoing AF ablation were prospectively randomized to usual care (N = 33) or intervention (N = 32) group. In addition to usual care, the intervention consisted of an educational session, three consultations spread over 6 months and telephone accessibility coordinated by the APN. Primary outcome was the AF recurrence rate at 6-month follow-up. Secondary outcomes were lifestyle factors (alcohol intake, exercise, BMI, smoking), patient satisfaction and AF knowledge measured at 1 and 6 months between groups and within each group. Study demographics at 1 month were similar, except AF knowledge was higher in the intervention group (8.6 vs. 7, P = 0.001). At 6 months, AF recurrence was significantly lower in the intervention group (13.5 vs. 39.4%, P = 0.014). Between groups, patient satisfaction and AF knowledge were significantly higher in the intervention group, respectively, 9.4 vs. 8.7 (P < 0.001) and 8.6 vs. 7.0 out of 10 (P < 0.001). Within the intervention group, alcohol intake decreased from 3.9 to 2.6 units per week (P = 0.031) and physical activity increased from 224.4 ± 210.7 to 283.8 ± 169.3 (P = 0.048). No changes occurred within the usual care group. Assignment to the intervention group was the only protective factor for AF recurrence [Exp(B) 0.299, P = 0.04] in multivariable-adjusted analysis. CONCLUSION: Adding APN-led care after ablation of AF improves short-term clinical outcome, patient satisfaction and physical activity and decreases alcohol intake.

The present study investigates the added value of advanced practitioner nurse (APN)-led care consisting of an educational session, three consultations spread over 6 months and telephone accessibility coordinated by the APN in patients after ablation of atrial fibrillation (AF). Main findings are The addition of nurse-led care after ablation of AF improves short-term clinical outcome, patient satisfaction and physical activity and decreases alcohol intake.Our study shows that integrating nurse-led care in the post-AF ablation setting is a relatively simple to implement, low-cost intervention with a major impact on patient outcomes and quality of care. These findings encourage including nurse-led care into routine AF ablation follow-up.

Jet Ventilation Reduces Coronary Sinus Movement in Patients Undergoing Atrial Fibrillation Ablation: An Observational Crossover Study.

BACKGROUND: One of the reasons that high-frequency jet ventilation (HFJV) is used is due to the near immobility of thoracic structures. However, no study has quantified the movements of cardiac structures during HFJV compared with normal mechanical ventilation. METHODS: After ethical approval and written informed consent, we included 21 patients scheduled for atrial fibrillation ablation in this prospective crossover study. Each patient was ventilated with both normal mechanical ventilation and HFJV. During each ventilation mode, displacements of the cardiac structure were measured by the EnSite Precision mapping system using a catheter placed in the coronary sinus. RESULTS: The median [Q1-Q4] displacement was 2.0 [0.6-2.8] mm during HFJV and 10.5 [9.3-13.0] mm during conventional ventilation (p < 0.000001). CONCLUSION: This study quantifies the minimal movement of cardiac structures during HFJV compared to standard mechanical ventilation.

V̇/Q̇ Mismatch: A Novel Target for COPD Treatment.

In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have been reported in early and mild stages of the disease. Such derangements often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance. Although much attention has been paid to pharmacologic treatment of mechanical abnormalities in COPD (eg, bronchodilators to deflate the lungs), increasing neurochemical afferent activity, secondary to gas-exchange inefficiency, has remained elusive as a therapeutic target. Hence, in this invited review, we first summarize how dyspnea, leading to poor exercise tolerance in COPD, may be explained by an increased venous admixture resulting from low V˙A/Q˙c, or wasted ventilation related to high V˙A/Q˙c, or both. We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance that act primarily on V˙A (bronchodilators, antiinflammatory medications) or Q˙c (oral and inhaled vasodilators, almitrine, and supplemental oxygen). Finally, to address the current knowledge and health care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange inefficiency and activity-related dyspnea in COPD: (1) enhanced and deeper phenotyping of patients with COPD with V˙A/Q˙c abnormalities and (2) evaluation of existing and novel pharmacologic treatments to improve gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity.

Temperature-guided ablation with the second-generation cryoballoon for paroxysmal atrial fibrillation: 3-year follow-up in a multicenter experience.

PURPOSE: A strategy based on the attainment of the specific parameter of - 40 °C within the first 60 s during cryoenergy applications in the setting of cryoballoon ablation (CB-A) without the use of an inner lumen mapping catheter (ILMC) (Achieve; Medtronic, USA) for the visualization of real-time recordings (RTR) has been previously described. The latter has proven to be very effective in guaranteeing freedom from atrial arrhythmias in patients affected by paroxysmal atrial fibrillation (PAF) at 1-year follow-up. The purpose of this retrospective observational study was to evaluate the clinical outcomes of this strategy in a multicenter experience on a long-term follow-up of 3 years. METHODS: A total of 192 patients having undergone CB ablation for paroxysmal AF (PAF) starting from September 2015 to November 2016 that underwent a temperature-guided approach were included. RESULTS: Mean procedural time was 68.77 ± 18.88. The mean number of freezes in the LSPV was 1.2 ± 0.4, 1.2 ± 0.4 in the LIPV, 1.1 ± 0.4 in the RSPV, and 1.2 ± 0.4 in the RIPV. Considering a blanking period of 3 months, freedom from AF off-AAD was achieved in 77.6% (149/192) at mean 34.5 ± 5.5 months and median 35.1 months (IQR, 32.3-37.0 months) follow-up after 1 procedure. CONCLUSIONS: A temperature-guided approach affords freedom from AF at a 3-year follow-up period in a large majority of patients affected by PAF having undergone a single CB-A procedure.

A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future.

Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) - understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.

Dyspnea in COPD: New Mechanistic Insights and Management Implications.

Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This "dyspnea spiral" is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients' benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand-capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual.

Plasma metabolomics and clinical predictors of survival differences in COPD patients.

BACKGROUND: Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP's relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C). METHODS: We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography / mass spectometry (LC/MS, LC/MS2, GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors. RESULTS: There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics. CONCLUSIONS: A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death.

The effect of radiographic emphysema in assessing lung cancer risk.

PURPOSE: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial. METHODS: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Lung cancer risk scores were calculated using the Bach, PLCOm2012 and Liverpool Lung Project models. Risk of incident lung cancer diagnosis at the end of the study and number screened per incident lung cancer were compared between participants with and without radiographic emphysema. RESULTS: Radiographic emphysema was independently associated with nearly double the hazard of lung cancer diagnosis at both the second (T1) and third (T2) annual LDCT in all three risk models (HR range 1.9-2.0, p<0.001 for all comparisons). The number screened per incident lung cancer was considerably lower in participants with radiographic emphysema (62 vs 28 at T1 and 91 vs 40 at T2). CONCLUSION: Radiographic emphysema is an independent predictor of lung cancer diagnosis and may help guide decisions surrounding further screening for eligible patients.

Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort.

BACKGROUND: Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. METHODS AND FINDINGS: We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. CONCLUSION: Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age.

Acute pericarditis following second-generation cryoballoon ablation for atrial fibrillation.

PURPOSE: Acute pericarditis is a minor complication following atrial fibrillation (AF) ablation procedures. The aim of the study was to evaluate the incidence and clinical aspects of pericarditis following cryoballoon (CB) ablation of AF investigating a possible association with procedural characteristics and a possible relationship with post-ablation recurrences. METHODS: Four hundred fifty consecutive patients (male 73%, age 59.9 ± 11.2 years) with drug-resistant paroxysmal AF who underwent CB ablation as index procedure were enrolled. Exclusion criteria were any contraindication for the procedure including the presence of intracavitary thrombus and uncontrolled heart failure and contraindications to general anesthesia. RESULTS: Acute pericarditis following CB ablation occurred in 18 patients (4%) of our study population. Pericardial effusion occurred in 14 patients (78%) and was mild/moderate. The total number of cryoapplications and the total freeze duration were significantly higher in patients with pericarditis compared with those without (respectively, p = 0.0006 and p = 0.01). Specifically, the number of applications and freeze duration in right inferior pulmonary vein were found significantly higher in patients with pericarditis (p = 0.007). The recurrence rate did not significantly differ between the two study groups (respectively, 16.7 vs 18.1%; p = 0.9). CONCLUSIONS: The incidence of acute pericarditis following CB ablation in our study population accounted for 4% and was associated with both total freezing time and number of cryoapplications. The clinical course was favorable in all these patients and the occurrence of acute pericarditis did not affect the outcome during the follow-up period.

Long-term outcome of pulmonary vein isolation in patients with paroxysmal atrial fibrillation and Brugada syndrome.

Aims: The therapeutical management of atrial fibrillation (AF) in the setting of Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs) with sodium channel blocking properties might lead to to the development of ventricular arrhythmias. This study sought to evaluate the clinical outcome in a consecutive series of patients with BS having undergone pulmonary vein (PV) isolation by means of radiofrequency (RF) or cryoballoon (CB) ablation and the efficacy of catheter ablation for preventing inappropriate interventions delivered by implantable cardioverter defibrillators (ICD) on a 3-year follow up. Methods and results: Twenty-three consecutive patients with BS (13 males; mean age was 47 ± 18 years) having undergone PV isolation for drug-resistant paroxysmal AF were enrolled. Eleven patients (48%) had an ICD implanted of whom four had inappropriate shocks secondary to rapid AF. Over a mean follow-up period of 35.0 ± 25.4 months (median 36 months) the freedom from AF recurrence after the index PV isolation procedure was 74% without AADs. Patients with inappropriate ICD interventions for AF did not present futher ICD shocks after AF ablation. No major complications occurred. Conclusion: Catheter ablation is a valid therapeutic choice for patients with BS and paroxysmal AF considering the high success rates, the limitations of the AADs and the safety of the procedure, and it should be taken into consideration especially in those patients presenting inappropriate ICD shocks due to rapid AF.

Role of Electrocardiographic Tpeak-Tend for the Prediction of Ventricular Arrhythmic Events in the Brugada Syndrome.

Some previous studies have proposed the electrocardiographic Tpeak-Tend (TpTe) as a possible predictor of ventricular arrhythmic events in patients with Brugada syndrome (BrS). We sought to analyze the association between the parameters of repolarization dispersion (TpTe, TpTe/QT, TpTe dispersion, QTc, and QTd) and ventricular fibrillation/sudden cardiac death in a large cohort of patients with type 1 BrS. A total of 448 consecutive patients with BrS (men 61%, age 45 ± 16 years) with spontaneous (n = 96, 21%) or drug-induced (n = 352, 79%) type 1 electrocardiogram were retrospectively included. At the time of the diagnosis or during a mean follow-up of 93 ± 47 months (median 88 months), 43 patients (9%) documented ventricular arrhythmias. No significant difference was observed in TpTe, TpTe/QT, maximum TpTe, and TpTe dispersion between asymptomatic patients and those with syncope and malignant arrhythmias. TpTe/QT ratio did not also significantly differ between patients with ventricular fibrillation/sudden cardiac death and those asymptomatic ones. In conclusion, TpTe was not significantly prolonged in those patients with type 1 BrS presenting with unexplained syncope or malignant arrhythmic events during follow-up.

Comparison of the Incidences of Complications After Second-Generation Cryoballoon Ablation of Atrial Fibrillation Using Vitamin K Antagonists Versus Novel Oral Anticoagulants.

Data evaluating the impact of the periprocedural administration of novel oral anticoagulants (NOACs) on complications in the setting of pulmonary vein (PV) isolation using cryoballoon (CB) is limited. In the present study, our aim was to analyze procedural characteristics and incidence of complications in those patients who underwent CB ablation for atrial fibrillation and the impact of NOACs on adverse events compared with vitamin K antagonists (VKAs). Consecutive patients with drug resistant atrial fibrillation who underwent PV isolation by CB as index procedure were retrospectively included in our analysis. In group I, 290 of 454 patients (63.9%) received VKAs (warfarin: n = 222 and acenocoumarol: n = 68), and in group II, 164 of 454 patients (36.1%) were treated with NOACs (rivaroxaban: n = 71; dabigatran: n = 60; and apixaban: n = 33). Age was significantly higher in the group II (62.8 ± 9.7 vs 58.6 ± 11.3; p <0.001). During the study period, 454 consecutive patients (male 71%, age 60.1 ± 10.9 years) were enrolled. Major complications occurred in 9 patients (2.0%): peripheral vascular complications were observed in 6 patients (1.3% per procedure), persistent phrenic nerve palsy occurred in 2 (0.4%), and transient ischemic attacks in 1 (0.2%). In both groups, the incidence of major complications was similar (group I [VKAs]: 7 patients [2.4%] vs group II [NOACs]: 2 patients [1.2%]; p = 0.5). In conclusion, CB ablation is a safe procedure for PV isolation and is associated with low complication rates. The incidence of adverse events in PV isolation using the second-generation CB with the periprocedural administration of NOACs is not significantly different than VKA treatment.

Second-generation cryoballoon ablation without the use of real-time recordings: A novel strategy based on a temperature-guided approach to ablation.

BACKGROUND: The achievement of -40°C within the first 60 seconds during cryoenergy applications has proven to independently predict durable pulmonary vein (PV) isolation in the setting of second-generation cryoballoon (CB-A; Medtronic, Minneapolis, MN) ablation. OBJECTIVE: We sought to evaluate a strategy based on the attainment of the specific parameter of -40°C within the first 60 seconds during cryoenergy applications in the setting of CB-A ablation without the use of an inner lumen mapping catheter (Achieve, Medtronic) for the visualization of real-time recordings. METHODS: A total of 52 patients having undergone CB ablation for paroxysmal atrial fibrillation (AF) between 1 February 2015 and 30 June 2015 who underwent a temperature-guided approach based on achieving -40°C within 60 seconds without real-time recordings (wire group) were compared with a cohort of 52 propensity score-matched patients having undergone CB ablation performed with an inner lumen mapping catheter (Achieve group). All PVs were checked for electrical isolation at the end of the procedure with a circular mapping catheter in the wire group. RESULTS: Electrical isolation could be obtained in all patients in the Achieve group and in 99% of PVs in the wire group. Freedom from AF without antiarrhythmic drugs at a mean follow-up of 12.4 ± 3.0 months did not significantly differ between both groups (85% vs 88%, respectively; P = .56). CONCLUSION: A temperature-guided approach based on achieving -40°C within 60 seconds is effective in producing PV isolation and affords freedom from AF at 12-month follow-up in 85% of patients affected by paroxysmal AF after a 3-month blanking period.

Distribution and Outcomes of a Phenotype-Based Approach to Guide COPD Management: Results from the CHAIN Cohort.

RATIONALE: The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. OBJECTIVE: We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. METHODS: We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. RESULTS: Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. CONCLUSIONS: There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use.