Exercise echocardiography to assess left atrial function in patients with symptomatic AF.

Background: Left atrial (LA) function contributes to the augmentation of cardiac output during exercise. However, LA response to exercise in patients with atrial fibrillation (AF) is unknown. We explored the LA mechanical response to exercise and the association between LA dysfunction and exercise intolerance. Methods: We recruited consecutive patients with symptomatic AF and preserved left ventricular ejection fraction (LVEF). Participants underwent exercise echocardiography and cardiopulmonary exercise testing (CPET). Two-dimensional and speckle-tracking echocardiography were performed to assess LA function at rest and during exercise. Participants were grouped according to presenting rhythm (AF vs sinus rhythm). The relationship between LA function and cardiorespiratory fitness in patients maintaining SR was assessed using linear regression. Results: Of 177 consecutive symptomatic AF patients awaiting AF ablation, 105 met inclusion criteria; 31 (29.5 %) presented in AF whilst 74 (70.5 %) presented in SR. Patients in SR augmented LA function from rest to exercise, increasing LA emptying fraction (LAEF) and LA reservoir strain. In contrast, patients in AF demonstrated reduced LAEF and reservoir strain at rest, with failure to augment either parameter during exercise. This was associated with reduced VO2Peak compared to those in SR (18.4 ± 5.6 vs 22.5 ± 7.7 ml/kg/min, p = 0.003). In patients maintaining SR, LAEF and reservoir strain at rest and during exercise were associated with VO2Peak, independent of LV function. Conclusion: The maintenance of SR in patients with AF is associated with greater LA reservoir function at rest and greater augmentation with exercise compared to patients in AF. In patients in SR, reduced LA function is associated with reduced exercise tolerance, independent of LV function.

APOLLO: A genome-scale metabolic reconstruction resource of 247,092 diverse human microbes spanning multiple continents, age groups, and body sites.

Computational modelling of microbiome metabolism has proved instrumental to catalyse our understanding of diet-host-microbiome-disease interactions through the interrogation of mechanistic, strain- and molecule-resolved metabolic models. We present APOLLO, a resource of 247,092 human microbial genome-scale metabolic reconstructions spanning 19 phyla and accounting for microbial genomes from 34 countries, all age groups, and five body sites. We explored the metabolic potential of the reconstructed strains and developed a machine learning classifier able to predict with high accuracy the taxonomic strain assignments. We also built 14,451 sample-specific microbial community models, which could be stratified by body site, age, and disease states. Finally, we predicted faecal metabolites enriched or depleted in gut microbiomes of people with Crohn's disease, Parkinson disease, and undernourished children. APOLLO is compatible with the human whole-body models, and thus, provide unprecedented opportunities for systems-level modelling of personalised host-microbiome co-metabolism. APOLLO will be freely available under https://www.vmh.life/.

Identification of Subclinical Heart Failure With Preserved Ejection Fraction in Patients With Symptomatic Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria. OBJECTIVES: The authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients. METHODS: Consecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire. RESULTS: Of 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF. CONCLUSIONS: Subclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

Influence of sex on efficacy of exercise training for patients with symptomatic atrial fibrillation: insights from the ACTIVE-AF randomized controlled trial.

AIMS: Exercise training reduces recurrence of arrhythmia and symptom severity amongst patients with symptomatic, non-permanent atrial fibrillation (AF). However, there is little evidence on whether this effect is modified by patient sex. In a sub-analysis from the ACTIVE-AF (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation) randomized controlled trial, we compared the effects of exercise training on AF recurrence and symptom severity between men and women. METHODS AND RESULTS: The ACTIVE-AF study randomized 120 patients (69 men, 51 women) with paroxysmal or persistent AF to receive an exercise intervention combining supervised and home-based aerobic exercise over 6 months or to continue standard medical care. Patients were followed over a 12-month period. The co-primary outcomes were recurrence of AF, off anti-arrhythmic medications and without catheter ablation, and AF symptom severity scores. By 12 months, recurrence of AF was observed in 50 (73%) men and 34 (67%) women. In an intention-to-treat analysis, there was a between-group difference in favour of the exercise group for both men [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.29-0.91, P = 0.022] and women (HR 0.47, 95% CI: 0.23-0.95, P = 0.035). At 12 months, symptom severity scores were lower in the exercise group compared with controls amongst women but not for men. CONCLUSION: An exercise-based intervention reduced arrhythmia recurrence for both men and women with symptomatic AF. Symptom severity was reduced with exercise in women at 12 months. No difference was observed in symptom severity for men. REGISTRATION: Australia and New Zealand Clinical Trials Registry: ACTRN12615000734561.

This analysis examined the potential benefit of exercise training on arrhythmia recurrence and symptom severity amongst men and women with symptomatic atrial fibrillation enrolled in a randomized controlled trial of exercise and physical activity intervention compared with standard medical care. Previous studies have not provided evidence on whether men and women might benefit from exercise training to a similar degree. Our findings highlight the following key points: Both men and women in our study experienced fewer arrhythmia recurrences with exercise training compared with men and women in standard medical care.Exercise reduced arrhythmia symptoms in women, but we did not find any evidence of a reduction in symptoms amongst men.

Associations of dietary patterns, ultra-processed food and nutrient intake with incident atrial fibrillation.

OBJECTIVE: To examine the associations between specific dietary patterns and incident atrial fibrillation (AF). METHODS: Using data from the UK Biobank, dietary intakes were calculated from 24-hour diet recall questionnaires. Indices representing adherence to dietary patterns (Mediterranean-style, Dietary Approaches to Stop Hypertension (DASH) and plant-based diets) were scored, and ultra-processed food consumption was studied as a percentage of total food mass consumed. Incident AF hospitalisations were assessed in Cox regression models. RESULTS: A total of 121 300 individuals were included, with 4 579 incident AF cases over a median follow-up of 8.8 years. Adherence to Mediterranean-style or DASH diets was associated with a lower incidence of AF in minimally adjusted analyses (HR for highest vs lowest quintile 0.87 (95% CI 0.80-0.96) and HR 0.78 (95% CI 0.71-0.86), respectively). However, associations were no longer significant after accounting for lifestyle factors (HR 0.95 (95% CI 0.87-1.04) and 0.94 (95% CI 0.86-1.04) respectively), with adjustment for body mass index responsible for approximately three-quarters of the effect size attenuation. Plant-based diets were not associated with AF risk in any models. Greatest ultra-processed food consumption was associated with a significant increase in AF risk even in fully adjusted models (HR 1.13 (95% CI 1.02-1.24)), and a 10% increase in absolute intake of ultra-processed food was associated with a 5% increase in AF risk (HR 1.05 (95% CI 1.01-1.08)). CONCLUSION: With the possible exception of reducing ultra-processed food consumption, these findings suggest that attention to other modifiable risk factors, particularly obesity, may be more important than specific dietary patterns for the primary prevention of AF.

Poor health-related quality of life in postural orthostatic tachycardia syndrome in comparison with a sex- and age-matched normative population.

PURPOSE: The effect of postural orthostatic tachycardia syndrome (POTS) on health-related quality of life (HrQoL) remains poorly studied. Here, we sought to compare the HrQoL in individuals with POTS to a normative age-/sex-matched population. METHODS: Participants enrolled in the Australian POTS registry between 5 August 2021 and 30 June 2022 were compared with propensity-matched local normative population data from the South Australian Health Omnibus Survey. The EQ-5D-5L instrument was used to assess HrQoL across the five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with global health rating assessed with a visual analog scale (EQ-VAS). A population-based scoring algorithm was applied to the EQ-5D-5L data to calculate utility scores. Hierarchical multiple regression analyses were undertaken to explore predictors of low utility scores. RESULTS: A total of 404 participants (n = 202 POTS; n = 202 normative population; median age 28 years, 90.6% females) were included. Compared with the normative population, the POTS cohort demonstrated significantly higher burden of impairment across all EQ-5D-5L domains (all P < 0.001), lower median EQ-VAS (p < 0.001), and lower utility scores (p < .001). The lower EQ-VAS and utility scores in the POTS cohort were universal in all age groups. Severity of orthostatic intolerance symptoms, female sex, fatigue scores, and comorbid diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were independent predictors of reduced HrQoL in POTS. The disutility in those with POTS was lower than many chronic health conditions. CONCLUSIONS: This is the first study to demonstrate significant impairment across all subdomains of EQ-5D-5L HrQoL in the POTS cohort as compared with a normative population. TRIAL REGISTRATION: ACTRN12621001034820.

High Incidence of Autonomic Dysfunction and Postural Orthostatic Tachycardia Syndrome in Patients with Long COVID: Implications for Management and Health Care Planning.

BACKGROUND: Autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), has been reported in individuals with post-acute sequelae of COVID-19 (PASC). However, the degree of dysautonomia in PASC has not been compared to those with POTS and healthy controls. METHODS: All participants were prospectively enrolled between August 5, 2021 and October 31, 2022. Autonomic testing included beat-to-beat hemodynamic monitoring to assess respiratory sinus arrhythmia, Valsalva ratio, and orthostatic changes during a 10-minute active standing test, as well as sudomotor assessment. The Composite Autonomic Symptom Score (COMPASS-31) was used to assess symptoms and the EuroQuol 5-Dimension survey (EQ-5D-5L) was used to assess health-related quality of life (HrQoL) measures. RESULTS: A total of 99 participants (n = 33 PASC, n = 33 POTS, and n = 33 healthy controls; median age 32 years, 85.9% females) were included. Compared with healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (P < .001), greater heart rate increase during 10-minute active standing test (P < .001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all P < .001), and poor HrQoL across all EQ-5D-5L domains (all P < .001), lower median EuroQol-visual analogue scale (P < .001), and lower utility scores (P < .001). The majority (79%) of those with PASC met the internationally established criteria for POTS. CONCLUSION: The prevalence of autonomic symptomology for POTS was high in those with PASC, leading to poor HrQoL and high health disutility. Autonomic testing should be routinely undertaken in those with PASC to aid diagnosis and direct appropriate management to improve health outcomes.

An Exercise and Physical Activity Program in Patients With Atrial Fibrillation: The ACTIVE-AF Randomized Controlled Trial.

BACKGROUND: There are limited data on the effect of exercise interventions on atrial fibrillation (AF) recurrence and symptoms. OBJECTIVES: The aim of this study was to determine the efficacy of an exercise and physical activity intervention on AF burden and symptoms among patients with symptomatic AF. METHODS: This prospective, randomized controlled trial included 120 patients with paroxysmal or persistent, symptomatic AF, randomized 1:1 to receive an exercise intervention, combining home and supervised aerobic exercise over 6 months, or to receive usual care. The coprimary outcomes were: 1) AF recurrence, off antiarrhythmic medications and without catheter ablation; and 2) symptom severity assessed by using a validated questionnaire. RESULTS: By 12 months, freedom from AF was achieved in 24 (40%) of 60 patients in the exercise group and 12 (20%) of 60 patients in the control group (HR: 0.50: 95% CI: 0.33 to 0.78). At 6 months, AF symptom severity was lower in the exercise group compared with the control group (mean difference -2.3; 95% CI: -4.3 to -0.2; P = 0.033). This difference persisted at 12 months (-2.3; 95% CI: -4.5 to -0.1; P = 0.041). Total symptom burden was lower at 6 months in the exercise group but not at 12 months. Peak oxygen consumption was increased in the exercise group at both 6 and 12 months. There were no between-group differences in cardiac structure or function, body mass index, or blood pressure. CONCLUSIONS: Participation in an exercise-based intervention over 6 months reduced arrhythmia recurrence and improved symptom severity among patients with AF. (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation [the ACTIVE-AF Study]; ACTRN12615000734561).

Trends in myocardial infarction and coronary revascularisation procedures in Australia, 1993-2017.

OBJECTIVE: Prior data have shown rising acute myocardial infarction (MI) trends in Australia; whether these increases have continued in recent years is not known. This study thus sought to characterise contemporary nationwide trends in MI hospitalisations and coronary procedures in Australia and their associated economic burden. METHODS: The primary outcome measure was the incidence and time trends of total MI, ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) hospitalisations from 1993 to 2017. The incidence and time trends of coronary procedures were additionally collected, alongside MI hospitalisation costs. RESULTS: Adjusted for population changes, annual MI incidence increased from 216.2 cases per 100 000 to a peak of 270.4 in 2007 with subsequent decline to 218.7 in 2017. Similarly, NSTEMI incidence increased from 68.0 cases per 100 000 in 1993 to a peak of 192.6 in 2007 with subsequent decline to 162.6 in 2017. STEMI incidence decreased from 148.3 cases per 100 000 in 1993 to 56.2 in 2017. Across the study period, there were annual increases in MI hospitalisations of 0.7% and NSTEMI hospitalisations of 5.6%, and an annual decrease in STEMI hospitalisations of 4.8%. Angiography and percutaneous coronary intervention increased by 3.4% and 3.3% annually, respectively, while coronary artery bypass graft surgery declined by 2.2% annually. MI hospitalisation costs increased by 100% over the study period, despite a decreased average length of stay by 45%. CONCLUSIONS: The rising incidence of MI hospitalisations appear to have stabilised in Australia. Despite this, associated healthcare expenditure remains significant, suggesting a need for continual implementation of public health policies and preventative strategies.

Use of heart rate for guiding exercise training in patients with atrial fibrillation.

BACKGROUND: Heart rate reserve (HRR) is used to guide exercise training in patients with cardiovascular disease, primarily as a surrogate for oxygen uptake reserve (VO2R) as a marker of metabolic demand. However, the relationship between HRR and VO2R in patients with atrial fibrillation (AF) is not well described. We aimed to assess the validity of HRR as a surrogate for VO2R to guide exercise intensity in AF patients. METHODS: One hundred one patients with non-permanent AF undertaking a cardiopulmonary exercise test (CPET) were prospectively enrolled. HR and VO2 values were recorded throughout exercise to determine HRR and VO2R at each workload. Linear regression was used to calculate the slope and y-intercept for HRR versus VO2R with an equivalent slope defined as 1 and y-intercept of 0. The impact of rhythm during exercise, beta blockers and chronotropic incompetence (CI) on the HRR-VO2R relationship was also assessed. RESULTS: The slope of HRR-VO2R was 0.79±0.4, indicating a significant difference from an assumed slope of 1.0 (mean difference: -0.21, 95% CI: -0.30 to -0.12, P<0.001). The mean y-intercept slope was 20.1±41.6, differing significantly from 0 (mean difference: 20.1, 95% CI: 11.9-28.3, P<0.001). The presence of AF during CPET, beta-blockers or chronotropic incompetence did not independently alter the association between VO2R and HRR. CONCLUSIONS: HRR is not equivalent to VO2R in AF patients. There was no significant effect of rhythm status, chronotropic incompetence or beta-blockers on this relationship. These findings highlight that the HR prescription of exercise intensity in AF patients should be guided by an individualised HRR-VO2R relationship.

Lifestyle Modification and Atrial Fibrillation: Critical Care for Successful Ablation.

Management of atrial fibrillation (AF) requires a comprehensive approach due to the limited success of medical or procedural approaches in isolation. Multiple modifiable risk factors contribute to the development and progression of the underlying substrate, with a heightened risk of progression evident with inadequate risk factor management. With increased mortality, stroke, heart failure and healthcare utilisation linked to AF, international guidelines now strongly support risk factor modification as a critical pillar of AF care due to evidence demonstrating the efficacy of this approach. Effective lifestyle management is key to arrest and reverse the progression of AF, in addition to increasing the likelihood of freedom from arrhythmia following catheter ablation.

Anemia and iron deficiency in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.

Alcohol intake and bradyarrhythmia risk: a cohort study of 407 948 individuals.

AIMS: There is a paucity of epidemiological evidence on alcohol and the risk of bradyarrhythmias. We thus characterized associations of total and beverage-specific alcohol consumption with incident bradyarrhythmias using data from the UK Biobank. METHODS AND RESULTS: Alcohol consumption reported at baseline was calculated as UK standard drinks (8 g alcohol)/week. Bradyarrhythmia events were defined as sinus node dysfunction (SND), high-level atrioventricular block (AVB), and permanent pacemaker implantations. Outcomes were assessed through hospitalization and death records, and dose-response associations were characterized using Cox regression models with correction for regression dilution bias. We studied 407 948 middle-aged individuals (52.4% female). Over a median follow-up time of 11.5 years, a total of 8 344 incident bradyarrhythmia events occurred. Increasing total alcohol consumption was not associated with an increased risk of bradyarrhythmias. Beer and cider intake were associated with increased bradyarrhythmia risk up to 12 drinks/week; however, no significant associations were observed with red wine, white wine, or spirit intake. When bradyarrhythmia outcomes were analysed separately, a negative curvilinear was observed for total alcohol consumption and risk of SND, but no clear association with AVB was observed. CONCLUSION: In this predominantly White British cohort, increasing total alcohol consumption was not associated with an increased risk of bradyarrhythmias. Associations appeared to vary according to the type of alcoholic beverage and between different types of bradyarrhythmias. Further epidemiological and experimental studies are required to clarify these findings.

Sex disparities in enrollment and reporting of outcomes by sex in contemporary clinical trials of atrial fibrillation.

BACKGROUND: Underrepresentation of females in randomized controlled trials (RCTs) limits generalizability and quality of the evidence guiding treatment of females. This study aimed to measure the sex disparities in participants' recruitment in RCTs of atrial fibrillation (AF) and determine associated factors, and to describe the frequency of outcomes reported by sex. METHODS: MEDLINE was searched to identify RCTs of AF published between January 1, 2011, and November 20, 2021, in 12 top-tier journals. We measured the enrollment of females using the enrollment disparity difference (EDD) which is the difference between the proportion of females in the trial and the proportion of females with AF in the underlying general population (obtained from the Global Burden of Disease). Random-effects meta-analyses of the EDD were performed, and multivariable meta-regression was used to explore factors associated with disparity estimates. We also determined the proportion of trials that included sex-stratified results. RESULTS: Out of 1133 records screened, 142 trials were included, reporting on a total of 133 532 participants. The random-effects summary EDD was -0.125 (95% confidence interval [CI] = -0.143 to -0.108), indicating that females were under-enrolled by 12.5 percentage points. Female enrollment was higher in trials with higher sample size (<250 vs. >750, adjusted odds ratio [aOR] 1.065, 95% CI: 1.008-1.125), higher mean participants' age (aOR: 1.006, 95% CI: 1.002-1.009), and lower in trials conducted in North America compared to Europe (aOR: 0.945, 95% CI: 0.898-0.995). Only 36 trials (25.4%) reported outcomes by sex, and of these 29 (80.6%) performed statistical testing of the sex-by-treatment interaction. CONCLUSION: Females remain substantially less represented in RCTs of AF, and sex-stratified reporting of primary outcomes is infrequent. These findings call for urgent action to improve sex equity in enrollment and sex-stratified outcomes' reporting in RCTs of AF.